ヨコヤ アキナリ
横谷 明徳教授
Akinari Yokoya

■研究者基本情報

組織

  • 理学部 理学科 生物科学コース
  • 理工学研究科(博士前期課程) 量子線科学専攻
  • 理工学研究科(博士後期課程) 量子線科学専攻
  • 基礎自然科学野 生物科学領域

研究分野

  • ライフサイエンス, 生物物理学
  • 環境・農学, 化学物質影響

研究キーワード

  • 量子生命科学
  • システム生物学
  • シンクロトロン放射
  • DNA損傷の物理化学的過程
  • クラスターDNA損傷
  • DNA修復
  • 放射線DNA損傷
  • 放射線生物物理学

学位

  • 1992年01月 博士(理学)(筑波大学)

学歴

  • 1992年01月, 筑波大学大学院, 博士(理学)修得
  • 1987年04月 - 1991年03月, 筑波大学大学院(博士課程後期), 生物科学研究科, 生物物理化学専攻(単位取得退学)
  • 1985年04月 - 1987年03月, 筑波大学大学院(博士課程前期), 生物科学研究科, 生物物理化学専攻
  • 1981年04月 - 1985年03月, 筑波大学, 第二学群, 生物学類

経歴

  • 2022年04月 - 現在, 国立研究開発法人 量子科学技術研究開発機構, 量子生命・医学部門 量子生命科学研究所 量子生命科学研究拠点センター, 専門業務員, 量子生命拠点特別コーディネーター、博士(理学)
  • 2021年04月 - 現在, 茨城大学, 大学院理工学研究科 量子線科学専攻, 教授(クロスアポイントメント)
  • 2021年06月 - 2022年03月, 国立研究開発法人量子科学技術研究開発機構, 量子生命・医学部門 量子生命研究所, 統括グループリーダー, 博士(理学)
  • 2019年04月 - 2021年03月, 国立研究開発法人量子科学技術研究開発機構, 量子生命科学領域, 上席研究員・統括グループリーダー
  • 2010年04月 - 2021年03月, 茨城大学大学院, 理工学研究科, 客員教授
  • 2016年04月 - 2019年03月, 国立研究開発法人量子科学技術研究開発機構, 東海量子ビーム応用研究センター, 上席研究員
  • 2012年04月 - 2016年03月, 独立行政法人日本原子力研究開発機構, 研究主席
  • 2004年04月 - 2012年03月, 独立行政法人日本原子力研究開発機構, 先端基礎研究センター, 研究主幹
  • 2008年04月 - 2010年03月, 茨城大学, 理学部, 特任教授
  • 2001年04月 - 2004年03月, 日本原子力研究所, 放射光科学研究センター, 副主任研究員
  • 2000年03月 - 2001年03月, 英国医学研究機構(MRC)客員研究員, 放射線とゲノム安定化ユニット, 客員研究員
  • 1991年04月 - 2000年03月, 日本原子力研究所, 大型放射光施設開発推進室, 研究員

委員歴

  • 2024年04月 - 現在, Photon Factory User Association 戦略・将来計画検討小委員会委員長, PF User association
  • 2023年12月 - 現在, Chair of Quantum Sensing Track of the organizing committee, The International Symposium on Quantum Sciece, Technology and Innovation (Quantum Innovation 2024)
  • 2012年 - 現在, PF-UA 運営委員, Photon Factory User Association
  • 2022年12月 - 2023年11月, Chair of Quantum Sensing Track of the organizing committee, The International Symposium on Quantum Sciece, Technology and Innovation (Quantum Innovation 2023)
  • 2022年01月 - 2022年11月, Chair of Quantum Sensing Track of the organizing committee, The International Symposium on Quantum Sciece, Technology and Innovation (Quantum Innovation 2022)
  • 2020年06月 - 2022年06月, 学術評議員, 日本放射線影響学会
  • 2021年05月 - 2021年12月, Track Chair of Quantum Sensing track of the organizing committee, The International Symposium on Quantum Sciece, Technology and Innovation (Quantum Innovation 2021)
  • 2019年05月 - 2020年05月, 評議員, 一般社団法人量子生命科学会
  • 2003年 - 2019年, Scientific Committee, International Symposium on the Physical, Molecular, Cellular and Medical Aspects of Auger Electron Process
  • 2013年 - 2017年11月, Scientific Comimittee, International Symposium on Microdosimetry (MICROS)
  • 2011年 - 2015年, Symposium Chair, International Symposium on the Physical, Molecular, Cellular and Medical Aspects of Auger Electron Process
  • 2012年01月 - 2013年12月, 評議員, 日本放射線影響学会
  • 2004年 - 2012年06月, Scientific Comimittee, International Workshop on Radiation Damage to DNA

■研究活動情報

受賞

  • 2022年06月, 第26回RADIOISOTOPES誌 論文奨励賞, マウス精巣器官培養法を活用した放射線不妊メカニズムの解析, 日本アイソトープ協会
    神長 輝一;横谷 明徳;福永 久典
  • 2020年12月, 優秀発表賞, X線照射ストレス下における細胞内Caイオンダイナミクスの測定法の検討, 量子生命科学会第2回大会
    鈴木碧海;横谷明徳
  • 2020年10月, 日本放射線影響学会賞, 放射線DNA損傷生成の物理化学的初期過程、及びマイクロビームとライブセル観察を組み合わせた細胞の放射線に対する応答システムの研究, 日本放射線影響学会
    横谷 明徳
  • 2019年05月, 優秀賞, X線小角散乱法によるDNA修復タンパク質(XRCC4)複合体形成過程の研究, 量子生命科学会第1回大会
    長谷川真保;西久保開;藤原悟;松尾龍人;横谷明徳

論文

  • Computational analysis of the spatial distributions of low-energy electrons generated via water photolysis and photoinjection into electrodes in water
    Takeshi Kai; Tomohiro Toigawa; Yusuke Matsuya; Yuho Hirata; Hidetsugu Tsuchida; Akinari Yokoya, ラスト(シニア)オーサー
    The Journal of Chemical Physics, 2025年04月21日, [査読有り]
  • チューブリン重合反応に対するX 線影響の検討 —インビトロ再構成実験系を用いたアプローチ—
    阿部紀宜; 清野良輔; 横谷明徳; 福永久典, Japan Radioisotope Association
    RADIOISOTOPES, 2025年03月15日, [査読有り]
  • Multiple DNA damages induced by water radiolysis demonstrated using a dynamic Monte Carlo code
    Takeshi Kai; Tomohiro Toigawa; Yusuke Matsuya; Yuho Hirata; Hidetsugu Tsuchida; Yuma Ito; Akinari Yokoya, ラスト(シニア)オーサー, Multiple DNA damage resulting from different nearby ionizations of water molecules is an important process of the initial step of radiobiological effects. Several important characteristics of the damaged DNA site such as the critical size and types of chemical lesions are not well-known. We investigated this long-term issue by developing a dynamic Monte Carlo code for the chemical process. The reaction probabilities and the spatial distribution of lesions were theoretically solved as a function of the spur radius and distance between DNA and the initial ionisation position. From our previous reported results, we suggest that a hydroxyl radical and a hydrated electron from a single spur can concomitantly react within a 10 base pairs DNA to induce a multiple DNA damage site comprising a DNA single-strand break and reductive nucleobase damage; however, the reaction probability is 0.4% or less. Once this combination arises, it may result in a DNA double-strand break (DSB). DSBs are difficult to repair, which may lead to cell death or misrepair, and could lead to point mutations in the genome., NATURE PORTFOLIO
    COMMUNICATIONS CHEMISTRY, 2025年03月06日, [査読有り]
  • Distribution of the dose response in a silicone-based radio-fluorogenic dosimeter and FWT-60 irradiated with monochromatic low-energy X-rays
    Seiko Nakagawa; Takuya Maeyama; Akinari Yokoya; Maki Ohara; Noriko Usami, Elsevier BV
    Radiation Measurements, 2025年02月, [査読有り]
  • Super-competition as a Novel Mechanism of the Dose-rate Effect in Radiation Carcinogenesis: A Mathematical Model Study.
    Yuya Hattori; Kento Nagata; Ritsuko Watanabe; Akinari Yokoya; Tatsuhiko Imaoka, Data from animal experiments show that the radiation-related risk of cancer decreases if the dose rate is reduced, even though the cumulative dose is unchanged (i.e., a dose-rate effect); however, the underlying mechanism is not well understood. To explore factors underlying the dose-rate effect observed in experimental rat mammary carcinogenesis, we developed a mathematical model that accounts for cellular dynamics during carcinogenesis, and then examined whether the model predicts cancer incidence. A mathematical model of multistage carcinogenesis involving radiation-induced cell death and mutagenesis was constructed using differential equations. The mutation rate was changed depending on the dose rate. The model also considered competition among cells with various mutation levels. The main parameters of the model were determined using previous experimental data. The parameters of the model were consistent with experimental observations. A dose-rate effect on carcinogenesis became apparent when the relationship between dose rate and mutation rate was linear quadratic or quadratic. The dose-rate effect became prominent when cells with more mutations preferentially compensated for the radiation-induced death of cells with fewer mutations. The phenomenon by which mutated cells gain a competitive advantage over normal cells is known as super-competition. Here, we identified super-competition as a novel mechanism underlying the dose-rate effects on carcinogenesis. The data also confirmed the relevance of the shape of the relationship between dose rate and the mutation rate. Thus, this study provides new evidence for the mechanism underlying the dose-rate effect, which is important for predicting the cancer-related risks of low-dose-rate irradiation.
    Radiation Research, 2025年01月20日, [査読有り]
  • Significant role of secondary electrons in the formation of a multi-body chemical species spur produced by water radiolysis
    Takeshi Kai; Tomohiro Toigawa; Yusuke Matsuya; Yuho Hirata; Tomoya Tezuka; Hidetsugu Tsuchida; Akinari Yokoya, ラスト(シニア)オーサー, Abstract

    Scientific insights into water photolysis and radiolysis are essential for estimating the direct and indirect effects of deoxyribonucleic acid (DNA) damage. Secondary electrons from radiolysis intricately associated with both effects. In our previous paper, we simulated the femtosecond (1 × 10− 15 s) dynamics of secondary electrons ejected by energy depositions of 11−19 eV into water via high-energy electron transport using a time-dependent simulation code. The results contribute to the understanding of simple “intra-spur” chemical reactions of tree-body chemical species (hydrated electrons, hydronium ion and OH radical) in subsequent chemical processes. Herein, we simulate the dynamics of the electrons ejected by energy depositions of 20−30 eV. The present results contribute to the understanding of complex “inter-spur” chemical reactions of the multi-body chemical species as well as for the formation of complex DNA damage with redox site and strand break on DNA. The simulation results present the earliest formation mechanism of an unclear multi-body chemical species spur when secondary electrons induce further ionisations or electronic excitations. The formation involves electron–water collisions, i.e. ionisation, electronic excitation, molecular excitation and elastic scattering. Our simulation results indicate that (1) most secondary electrons delocalise to ~ 12 nm, and multiple collisions are sometimes induced in a water molecule at 22 eV deposition energy. (2) The secondary electrons begin to induce diffuse band excitation of water around a few nm from the initial energy deposition site and delocalise to ~ 8 nm at deposition energies ~ 25 eV. (3) The secondary electron can cause one additional ionisation or electronic excitation at deposition energies > 30 eV, forming a multi-body chemical species spur. Thus, we propose that the type and density of chemical species produced by water radiolysis strongly depend on the deposition energy. From our results, we discuss formation of complex DNA damage., Springer Science and Business Media LLC
    Scientific Reports, 2024年10月21日, [査読有り]
  • Luminal progenitor and mature cells are more susceptible than basal cells to radiation-induced DNA double-strand breaks in rat mammary tissue.
    Kento Nagata; Mayumi Nishimura; Kazuhiro Daino; Yukiko Nishimura; Yuya Hattori; Ritsuko Watanabe; Daisuke Iizuka; Akinari Yokoya; Keiji Suzuki; Shizuko Kakinuma; Tatsuhiko Imaoka, Ionizing radiation promotes mammary carcinogenesis. Induction of DNA double-strand breaks (DSBs) is the initial event after radiation exposure, which can potentially lead to carcinogenesis, but the dynamics of DSB induction and repair are not well understood at the tissue level. In this study, we used female rats, which have been recognized as a useful experimental model for studying radiation effects on the mammary gland. We focused on differences in DSB kinetics among basal cells, luminal progenitor and mature cells in different parts of the mammary duct. 53BP1 foci were used as surrogate markers of DSBs, and 53BP1 foci in each mammary epithelial cell in immunostained tissue sections were counted 1-24 h after irradiation and fitted to an exponential function of time. Basal cells were identified as cytokeratin (CK) 14+ cells, luminal progenitor cells as CK8 + 18low cells and luminal mature cells as CK8 + 18high cells. The number of DSBs per nucleus tended to be higher in luminal cells than basal cells at 1 h post-irradiation. A model analysis indicated that basal cells in terminal end buds (TEBs), which constitute the leading edge of the mammary duct, had significantly fewer initial DSBs than the two types of luminal cells, and there was no significant difference in initial amount among the cell types in the subtending duct. The repair rate did not differ among mammary epithelial cell types or their locations. Thus, luminal progenitor and mature cells are more susceptible to radiation-induced DSBs than are basal cells in TEBs.
    Journal of Radiation Research, 2024年09月05日, [査読有り]
  • 〔主要な業績〕Consideration of the dielectric response for radiation chemistry simulations.
    Tomohiro Toigawa; Takeshi Kai; Yuta Kumagai; Akinari Yokoya, ラスト(シニア)オーサー, The spur reaction, a spatially nonhomogeneous chemical reaction following ionization, is crucial in radiolysis or photolysis in liquids, but the spur expansion process has yet to be elucidated. One reason is the need to understand the role of the dielectric response of the solvating molecules surrounding the charged species generated by ionization. The dielectric response corresponds to the time evolution of the permittivity and might affect the chemical reaction-diffusion of the species in a spur expansion process. This study examined the competitive relationship between reaction-diffusion kinetics and the dielectric response by solving the Debye-Smoluchowski equation while considering the dielectric response. The Coulomb force between the charged species gradually decreases with the dielectric response. Our calculation results found a condition where fast recombination occurs before the dielectric response is complete. Although it has been reported that the primary G-values of free electrons depend on the static dielectric constant under low-linear-energy transfer radiation-induced ionization, we propose that considering the dielectric response can provide a deeper insight into fast recombination reactions under high-linear-energy transfer radiation- or photo-induced ionization. Our simulation method enables the understanding of fast radiation-induced phenomena in liquids.
    The Journal of chemical physics, 2024年06月07日, [査読有り]
  • Ultrafast fragmentation of highly-excited doubly-ionized deoxyribose: role of the liquid water environment.
    Marie-Anne Hervé du Penhoat; Alexandre Souchaud; Aashini Rajpal; Rodolphe Vuilleumier; Marie-Pierre Gaigeot; Ivano Tavernelli; Kentaro Fujii; Akinari Yokoya; Sergio Díaz-Tendero; Marie-Françoise Politis, Ab initio molecular dynamics simulations are used to investigate the fragmentation dynamics following the double ionization of 2-deoxy-D-ribose (DR), a major component in the DNA chain. Different ionization scenarios are considered to provide a complete picture. First focusing on isolated DR2+, fragmentation patterns are determined for the ground electronic state, adding randomly distributed excitation energy to the nuclei. These patterns differ for the two isomers studied. To compare thermal and electronic excitation effects, Ehrenfest dynamics are also performed, allowing to remove the two electrons from selected molecular orbitals. Two intermediate-energy orbitals, localized on the carbon chain, were selected. The dissociation pattern corresponds to the most frequent pattern obtained when adding thermal excitation. On the contrary, targeting the four deepest orbitals, localized on the oxygen atoms, leads to selective ultrafast C-O and/or O-H bond dissociation. To probe the role of environment, a system consisting of a DR molecule embedded in liquid water is then studied. The two electrons are removed from either the DR or the water molecules directly linked to the sugar through hydrogen bonds. Although the dynamics onset is similar to that of isolated DR when removing the same deep orbitals localized on the sugar oxygen atoms, the subsequent fragmentation patterns differ. Sugar damage also occurs following the Coulomb explosion of neighboring H2O2+ molecules due to interaction with the emitted O or H atoms.
    Physical chemistry chemical physics : PCCP, 2024年05月29日, [査読有り]
  • Decomposition characteristics of a hypervalent iodine compound, 2-iodosobenzoic acid, exposed to monochromatic X-rays around the iodine L3-edge energy region
    Maki Ohara; Yudai Izumi; Hideo Takakura; Shosei Enomoto; Kentaro Fujii; Akinari Yokoya; Mikako Ogawa, Elsevier BV
    Radiation Physics and Chemistry, 2024年03月, [査読有り]
  • X-ray photoemission and absorption spectroscopy of a hypervalent iodine compound, 2-iodosobenzoic acid
    Yudai Izumi; Maki Ohara; Kentaro Fujii; Akinari Yokoya; Mikako Ogawa, Elsevier BV
    Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 2024年02月, [査読有り]
  • Electronic states of fluorinated DNA components revealed by X-ray photoelectron spectroscopy
    S. Onuma; Y. Izumi; M. Ohara; A. Yokoya, ラスト(シニア)オーサー
    Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 2024年02月, [査読有り]
  • ゲノムの構造と機能、およびエネルギー代謝に及ぼす 放射線の長期影響
    廣瀬 エリ; 横谷 明徳; 野口 実穂; Lucie Huar; 鈴木 啓司
    放射線生物研究, 2024年, [査読有り]
  • Comparison of core and valence band electronic structures of bulk uracil and 5-halouracils
    Yudai Izumi; Maki Ohara; Yuji Baba; Akinari Yokoya, ラスト(シニア)オーサー
    Physical Chemistry Chemical Physics, 2024年, [査読有り]
  • High linear energy transfer (LET) nature of alanine radical yield by soft X-ray irradiations studied by electron spin resonance (ESR) applications
    Seiko Nakagawa; Akinari Yokoya; Maki Ohara; Noriko Usami; Mizue Asada; Motoyasu Fujiwara; Toshikazu Nakamura; Kenji Ishikawa, Elsevier BV
    Radiation Physics and Chemistry, 2024年01月, [査読有り]
  • Temporal Dynamic Regulation of Autophagy and Senescence Induction in Response to Radiation Exposure.
    Miho Noguchi; Tomokazu Ihara; Keiji Suzuki; Akinari Yokoya, ラスト(シニア)オーサー, Autophagy and senescence are closely related cellular responses to genotoxic stress, and play significant roles in the execution of cellular responses to radiation exposure. However, little is known about their interplay in the fate-decision of cells receiving lethal doses of radiation. Here, we report that autophagy precedes the establishment of premature senescence in normal human fibroblasts exposed to lethal doses of radiation. Activation of the p53-dependent DNA damage response caused sustained dephosphorylation of RB proteins and consequent cell cycle arrest, concurrently with Ulk1 dephosphorylation at Ser638 by PPM1D, which promoted autophagy induction 1-2 days after irradiation. In addition, mitochondrial fragmentation became obvious 1-2 days after irradiation, and autophagy was further enhanced. However, Ulk1 levels decreased significantly after 2 days, resulting in lower LC3-II levels. An autophagic flux assay using chloroquine (CQ) also revealed that the flux in irradiated cells gradually decreased over 30 days. In contrast, lysosomal augmentation started at 1 day, became significantly upregulated after 5 days, and continued for over 30 days. After a rapid decrease in autophagy, p16 expression increased and senescence was established, but autophagic activity remained reduced. These results demonstrated that X-ray irradiation triggered two processes, autophagy and senescence, with the former being temporary and regulated by DNA damage response and mitophagy, and the latter being sustained and regulated by persistent cell cycle arrest. The interplay between autophagy and senescence seems to be essential for the proper implementation of the cellular response to radiation exposure.
    Radiation research, 2023年10月30日, [査読有り]
  • First-principles simulation of an ejected electron produced by monochromatic deposition energy to water at the femtosecond order.
    Takeshi Kai; Tomohiro Toigawa; Yusuke Matsuya; Yuho Hirata; Tomoya Tezuka; Hidetsugu Tsuchida; Akinari Yokoya, ラスト(シニア)オーサー, This study uses a time-dependent first-principles simulation code to investigate the transient dynamics of an ejected electron produced in the monochromatic deposition energy from 11 to 19 eV in water. The energy deposition forms a three-body single spur comprising a hydroxyl radical (OH˙), hydronium ion (H3O+), and hydrated electron (eaq-). The earliest formation involves electron thermalization and delocalization dominated by the molecular excitation of water. Our simulation results show that the transient electron dynamics primarily depends on the amount of deposition energy to water; the thermalization time varies from 200 to 500 fs, and the delocalization varies from 3 to 10 nm in this energy range. These features are crucial for determining the earliest single-spur formation and facilitating a sequential simulation from an energy deposition to a chemical reaction in water photolysis or radiolysis. The spur radius obtained from the simulation correlates reasonably with the experimental-based estimations. Our results should provide universalistic insights for analysing ultrafast phenomena dominated by the molecular excitation of water in the femtosecond order.
    RSC advances, 2023年10月29日, [査読有り]
  • 放射線DNA損傷の量子過程とその難修復性評価の試み
    横谷明徳, 筆頭著者, 放射線によるDNA損傷の物理化学的初期過程の解明は,低線量放射線のリスク評価のみならずメカニズムに基づいた放射線治療の基盤を提供すると考えられる。本稿ではミクロな世界を支配する量子的性質のひとつである電子物性に焦点を当て,DNA内に臭素(Br)原子を取り込ませた細胞の持つ大きな放射線増感の起源を,X線光電子分光による物理計測と量子化学計算の両面から探る研究を紹介する。さらにDNA損傷の難修復性を評価するための,EGFP発現プラスミドDNAを放射線照射した後非照射細胞へ導入する新しい試みについても併せて紹介する。(著者抄録), (株)北隆館
    Bio Clinica, 2023年08月, [招待有り]
  • X-ray irradiation-induced ligand cleavage of a phthalocyanine derivative, tin (IV) phthalocyanine dichloride: A potential for X-ray activation of caged compounds
    Yudai Izumi; Maki Ohara; Kentaro Fujii; Akinari Yokoya; Mikako Ogawa, The X-ray dissociation of tin (IV) phthalocyanine dichloride (SnCl2Pc) was investigated using X-ray photoemission spectroscopy. The photoemission spectra of SnCl2Pc after X-ray irradiation exhibited additional components assigned as chloride ions and tin (II) phthalocyanine, as well as decomposition products from the phthalocyanine framework, indicating that X-ray irradiation induced the release of chloride ions as ligands from SnCl2Pc. Although the ligand releases were caused not by a simple cleavage between Cl-Sn bonding but by accompanying the molecular framework destruction, these reactions may robustly facilitate a novel application of X-rays to activate caged compounds in tissues.
    Chemical Physics Letters, 2023年07月, [査読有り]
  • 〔主要な業績〕Incorporation of a bromine atom into DNA-related molecules changes their electronic properties.
    Misaki Hirato; Akinari Yokoya; Yuji Baba; Seiji Mori; Kentaro Fujii; Shin-Ichi Wada; Yudai Izumi; Yoshinori Haga, 責任著者, To understand the mechanism underlying the high radio-sensitisation of living cells possessing brominated genomic DNA, X-ray photoelectron spectroscopy (XPS) using synchrotron X-rays with energies of 2000 or 2500 eV was used to study brominated and nonbrominated nucleobases, nucleosides and nucleotides. The bromine atom significantly reduced the energy gap between the valence and conduction states, although the core level states were not greatly affected. This finding was supported by quantum chemical calculation for the nucleobases and nucleosides. Our findings strongly indicate that the energy gaps between the valence and conduction levels of the molecules are significantly reduced by bromination. Furthermore, the brominated molecules are more likely to produce inelastic scattering low energy electrons upon exposure to 2000 or 3000 eV X-rays. This modification of electronic properties around the brominated group may both facilitate electron transfer to the brominated site in DNA and increase the probability of reaction with low energy electrons. These processes can induce DNA damage, presumably resulting in debromination of the uracil moiety and a subsequent cytotoxic effect.
    Physical chemistry chemical physics : PCCP, 2023年05月31日, [査読有り]
  • Structural study of wild-type and phospho-mimic XRCC4 dimer and multimer proteins using circular dichroism spectroscopy.
    Kai Nishikubo; Maho Hasegawa; Yudai Izumi; Kentaro Fujii; Koichi Matsuo; Yoshihisa Matsumoto; Akinari Yokoya, ラスト(シニア)オーサー, PURPOSE: To investigate the structural features of wild-type and phospho-mimicking mutated XRCC4 protein, a protein involved in DNA double-strand break repair. MATERIALS AND METHODS: XRCC4 with a HisTag were expressed by E. coli harboring plasmid DNA and purified. Phospho-mimicking mutants in which one phosphorylation site was replaced with aspartic acid were also prepared in order to reproduce the negative charge resulting from phosphorylation. The proteins were separated into dimers and multimers by gel filtration chromatography. Circular dichroism (CD) spectroscopy was performed in the region from ultraviolet to vacuum-ultraviolet. The CD spectra were analyzed with two analysis programs to evaluate the secondary structures of the wild-type and phospho-mimicked dimers and multimers. RESULT AND DISCUSSION: The proportion of β-strand in the wild-type dimers was very low, particularly in their C-terminal region, including the five phosphorylation sites. The secondary structure of the phospho-mimic hardly changed from the monomeric to dimeric forms. In contrast, the β-strand content increased and the α-helix content decreased upon multimerization of the wild-type protein. The structural change of multimers slightly depended on the phospho-mimic site. These results suggest that the β-strand structure stabilizes the multimerization of XRCC4 and it is regulated by phosphorylation at the C-terminal site in living cells. CONCLUSION: An increase in the β-strand content in XRCC4 is essential for stabilization of the multimeric form through C-terminal phosphorylation, allowing formation of the large double-strand break repair machinery.
    International journal of radiation biology, 2023年05月12日, [査読有り]
  • Nature of the physicochemical process in water photolysis uncovered by a computer simulation.
    Takeshi Kai; Tomohiro Toigawa; Masatoshi Ukai; Kentaro Fujii; Ritsuko Watanabe; Akinari Yokoya, ラスト(シニア)オーサー, In this work, we investigate the physicochemical process of water photolysis to bridge physical and chemical processes by a newly developed first-principles calculation code. The deceleration, thermalization, delocalization, and initial hydration of the extremely low-energy electrons ejected by water photolysis are sequentially tracked in the condensed phase. We show herein the calculated results for these sequential phenomena during 300 fs. Our results indicate that the mechanisms heavily depend on the intermolecular vibration and rotation modes peculiar to water and the momentum transfer between the electrons and the water medium. We suggest that using our results for the delocalized electron distribution will reproduce successive chemical reactions measured by photolysis experiments using a chemical reaction code. We expect our approach to become a powerful technique for various scientific fields related to water photolysis and radiolysis.
    The Journal of chemical physics, 2023年04月28日, [査読有り]
  • Secondary structural analyses of histone H2A-H2B proteins extracted from heated cells.
    Yudai Izumi; Koichi Matsuo; Akinari Yokoya, ラスト(シニア)オーサー, Histone proteins, building blocks of chromatins, participate in enzymatic reactions in cells heated at around 45°C though in vitro the denaturation of histones significantly proceeds at a similar temperature. It implies that unidentified mechanisms prevent thermal denaturation of histones in vivo. However, studies on the histone structures in the heated cells have been scarce. Here, we analyzed the secondary structures of histone H2A-H2B proteins originating from the heated cells using circular dichroism spectroscopy. The secondary structure contents of the H2A-H2B extracted from the heated cells differed from those of H2A-H2B both native and denatured in vitro but reverted to the native structures by incubating the heated cells at 37°C within 2 h. Such structural flexibility may play a role in protecting genomic functions governed by chromatin structures from heat stresses.
    Chirality, 2023年03月, [査読有り]
  • Initial yield of hydrated electron production from water radiolysis based on first-principles calculation
    Takeshi Kai; Tomohiro Toigawa; Yusuke Matsuya; Yuho Hirata; Tomoya Tezuka; Hidetsugu Tsuchida; Akinari Yokoya, ラスト(シニア)オーサー, For water radiolysis, conventional simulation methods estimate free radical yields based on the cross-sections. Our results indicated that electron dynamic motion must be further solved to predict the initial yields of hydrated electrons., Royal Society of Chemistry (RSC)
    RSC Advances, 2023年02月, [査読有り]
  • Mitochondrial Metabolism in X-Irradiated Cells Undergoing Irreversible Cell-Cycle Arrest.
    Eri Hirose; Miho Noguchi; Tomokazu Ihara; Akinari Yokoya, ラスト(シニア)オーサー, Irreversible cell-cycle-arrested cells not undergoing cell divisions have been thought to be metabolically less active because of the unnecessary consumption of energy for cell division. On the other hand, they might be actively involved in the tissue microenvironment through an inflammatory response. In this study, we examined the mitochondria-dependent metabolism in human cells irreversibly arrested in response to ionizing radiation to confirm this possibility. Human primary WI-38 fibroblast cells and the BJ-5ta fibroblast-like cell line were exposed to 20 Gy X-rays and cultured for up to 9 days after irradiation. The mitochondrial morphology and membrane potential were evaluated in the cells using the mitochondrial-specific fluorescent reagents MitoTracker Green (MTG) and 5,5',6,6'-tetraethyl-benzimidazolylcarbocyanine iodide (JC-1), respectively. The ratio of the mean MTG-stained total mitochondrial area per unit cell area decreased for up to 9 days after X-irradiation. The fraction of the high mitochondrial membrane potential area visualized by JC-1 staining reached its minimum 2 days after irradiation and then increased (particularly, WI-38 cells increased 1.8-fold the value of the control). Their chronological changes indicate that the mitochondrial volume in the irreversible cell-cycle-arrested cells showed significant increase concurrently with cellular volume expansion, indicating that the mitochondria-dependent energy metabolism was still active. These results indicate that the energy metabolism in X-ray-induced senescent-like cells is active compared to nonirradiated normal cells, even though they do not undergo cell divisions.
    International journal of molecular sciences, 2023年01月17日, [査読有り]
  • Analysis of differentially expressed genes on human X chromosome harboring large deletion induced by X-rays.
    Eri Hirose; Akinari Yokoya; Kasumi Kawamura; Keiji Suzuki, We examined here normal human cells with large deletions encompassing the hypoxanthine-phosphoribosyltransferase 1 (HPRT1) gene on X chromosome. Expression levels of genes on X chromosome were analyzed by microarray and RT-qPCR method, and differentially expressed genes (DEGs) were extracted. We found that DEGs were not limited to the genes flanking deleted regions but spread over the entire X chromosome. Interestingly, the gene regulation patterns were similar to a large extent among independent clones that have similar-sized large deletions involving the HPRT1 gene. Thus, it is indicated that an impact of large deletion on possible epigenetic transcriptional regulation is not limited to the regions proximal to the deletion region.
    Journal of radiation research, 2023年01月06日, [査読有り]
  • Core level ionization or excitation and Auger relaxation induce clustered DNA damage.
    Akinari Yokoya; Yui Obata, 筆頭著者, Ionizing radiation causes various types of DNA damage, such as single- (SSBs) and double-strand breaks (DSBs), nucleobase lesions, abasic sites (AP sites), and cross-linking between complementary strands of DNA or DNA and proteins. DSBs are among the most harmful type of DNA damage, inducing serious genetic effects such as cell lethality and mutation. Nucleobase lesions and AP sites, on the other hand, may be less deleterious and are promptly repaired by base excision repair (BER) pathways. Recently, biochemical approaches to quantify nucleobase lesions and AP sites have revealed certain types of non-strand break lesions as harmful DNA damage, called clustered DNA damage. Such clusters can retard nucleobase excision repair enzymes, and can sometimes be converted to DSBs by BER catalysis. This unique character of clustered DNA damage strongly depends on the spatial density of ionization or excitation events occurring at the track end of initial radiation or low energy secondary electrons. In particular, the photoelectric effect of elements comprising biological molecules, followed by emission of Auger electrons, are key factors in determining the future fate of each clustered damage site. This chapter describes biological studies of clustered nucleobase lesions with SSBs or AP sites, and mechanistical studies on core level excitation and Auger relaxation giving rise to clustered DNA damage.
    The Enzymes, 2022年10月07日, [査読有り], [招待有り]
  • X-ray photoelectron spectroscopy of Thymine and 5-Bromouracil studied by Symmetry-Adapted-Cluster Configuration-Interaction (SAC-CI) theory
    Yusaku I. Kurokawa; Hiroshi Nakatsuji; Misaki Hirato; Akinari Yokoya, ラスト(シニア)オーサー, Elsevier BV
    Chemical Physics Letters, 2022年10月, [査読有り]
  • Establishment of a Method for Investigating Direct and Indirect Actions of Ionizing Radiation Using Scavenger-free Plasmid DNA.
    Hao Yu; Yusuke Kondo; Kentaro Fujii; Akinari Yokoya; Shinichi Yamashita, In this study, an improved method using scavenger-free plasmid DNA was established to accurately determine yields of DNA damage induced by direct and indirect actions of ionizing radiation. The scavenger-free plasmid DNA was obtained by dialysis over 5-7 days, and the DNA solvent was replaced with phosphate buffer to completely remove impurities, which could be scavengers of radicals produced as a result of water radiolysis. DNA samples of films and dilute aqueous solutions were used to separately evaluate contributions of the direct and indirect actions of X rays (150-160 kVp). The irradiated DNA was analyzed by agarose gel electrophoresis to quantify strand-break yields. The yields of single-strand breaks (SSBs), n(SSB), were determined to be (6.5 ± 2.0) × 10-10 and (3.1 ± 0.9) × 10-7 SSBs/Gy/Da for the film and solution samples, respectively, showing a significant contribution of hydroxyl radicals (•OH) compared with direct energy depositions from ionizing radiation to DNA. As observed in SSBs, the yields of double-strand breaks (DSBs), n(DSB), were (5.6 ± 1.1) × 10-11 and (1.3 ± 0.2) × 10-8 DSBs/Gy/Da for the film and solution samples, respectively. The yield ratio of DSBs to SSBs, that is, n(DSB)/n(SSB), was 0.091 ± 0.026 for the film samples, while it was much lower for the solution samples (0.045 ± 0.010), indicating that direct actions result in more localized strand breaks relative to indirect actions. Base excision repair enzymes, namely, endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg), were utilized after irradiations to convert base lesions and apurinic/apyrimidinic (AP) sites into strand breaks. The amounts of Nth and Fpg for the conversion were optimized to a few units per µg of DNA, although the optimal concentrations can differ among conditions.
    Radiation Research, 2022年06月01日, [査読有り]
  • Molecular Interactions of Normal and Irradiated Tubulins During Polymerization
    Hisanori Fukunaga; Yuka Kimura; Ami Suzuki; Yuki Kawabata; Akinari Yokoya, ラスト(シニア)オーサー, Microtubules, one of the cytoskeletons, are highly dynamic structures that play a variety of roles in maintaining cell morphology, cell division and intracellular transport. Microtubules are composed of heterodimers of α- and β-tubulins, which are repeatedly polymerized and depolymerized. To investigate the radiation-induced impacts on the polymerization reaction of tubulins, we evaluated the molecular interactions between normal and irradiated tubulins. First, the polymerization reaction of the tubulins was measured after stepwise irradiation from 0 Gy to 1,000 Gy of X rays. The polymerization was inhibited in a dose-dependent manner. Next, the tubulins' polymerization reaction was then measured after the tubulin that was damaged from the exposure to 1,000 Gy of X rays was mixed with the normal tubulins. Our findings reveal that the radiation dose-dependent change in the degree of overall microtubule polymerization progression depends on the ratio of damaged tubulin. This result is biochemical evidence that non-DNA damage (in this case, cytoskeletal damage) from cytoplasmic radiation exposure may inhibit cell division, suggesting that some cytoskeletal damage may also affect the fate of the entire cell., Radiation Research Society
    Radiation Research, 2022年05月23日, [査読有り]
  • マウス精巣器官培養法を活用した放射線不妊メカニズムの解析
    神長輝一; 横谷明徳; 福永久典, Japan Radioisotope Association
    RADIOISOTOPES, 2022年03月15日, [査読有り], [招待有り]
  • A Brief Overview of Radiation-Induced Effects on Spermatogenesis and Oncofertility.
    Hisanori Fukunaga; Akinari Yokoya; Kevin M Prise, The genotoxicity of radiation on germ cells may be passed on to the next generation, thus its elucidation is not only a scientific issue but also an ethical, legal, and social issue in modern society. In this article, we briefly overview the effects of radiation on spermatogenesis and its associated genotoxicity, including the latest findings in the field of radiobiology. The potential role of transgenerational effects is still poorly understood, and further research in this area is desirable. Furthermore, from the perspective of oncofertility, we discuss the historical background and clinical importance of preserving male fertility during radiation treatment and the potential of microbeam radiotherapy. We hope that this review will contribute to stimulating further discussions and investigations for therapies for pediatric and adolescent/young adult patients.
    Cancers, 2022年02月04日, [査読有り]
  • No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields.
    Hisanori Fukunaga; Kiichi Kaminaga; Eri Hirose; Ritsuko Watanabe; Noriko Usami; Kevin M Prise; Akinari Yokoya, ラスト(シニア)オーサー, The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research. In this study, we investigated the non-targeted effects on the regulation of the cell cycle of human cervical carcinoma (HeLa) cells with imperfect p53 function that express the FUCCI (HeLa-FUCCI cells). The possible effects on the cell-cycle phases via soluble factors were analyzed following exposure to different field configurations, which were delivered using a 150 kVp X-ray irradiator. In addition, using synchrotron-generated, 5.35 keV monochromatic X-ray microbeams, high-precision 200 μm-slit microbeam irradiation was performed to investigate the possible impacts on the cell-cycle phases via cell-cell contacts. Collectively, we could not detect the intercellular regulation of the cell cycle in HeLa-FUCCI cells, which suggested that the unregulated cell growth was a malignant tumor. Our findings indicated that there was no significant intercellular control system of the cell cycle in malignant tumors during or after radiotherapy, highlighting the differences between normal tissue and tumor characteristics.
    International journal of molecular sciences, 2021年11月26日, [査読有り]
  • 〔主要な業績〕Expression of an X-Ray Irradiated EGFP-Expressing Plasmid Transfected into Nonirradiated Human Cells.
    Yui Obata; Hiroki Nakaue; Keishiro Hirasaki; Nobuyoshi Akimitsu; Akinari Yokoya, ラスト(シニア)オーサー, To investigate the repairability of X-ray induced DNA damage, particularly non-double-strand breaks in living cells, enhanced green fluorescent protein (EGFP)-expressing plasmids X-ray irradiated and then transfected into nonirradiated human cells, MCF7 and MCF10A. Live-cell imaging of EGFP fluorescence was performed to measure the efficiency of plasmid repair in cells. The number of EGFP-expressing cells significantly decreased with increasing X-ray dose for both cell lines. The obtained kinetic curves of EGFP expression indicating plasmid repair were quantitatively compared against algebraically calculated ones based on the values of the transfected plasmids that had been treated with nicking or restriction enzymes. Then, assuming a Poisson distribution of single-strand breaks (SSBs), the number of cells carrying these nicked plasmids that could express EGFP were estimated. Our experimental results revealed considerably fewer cells expressing EGFP compared to the expected values we had calculated. These results suggest that the lower proportion of cells expressing EGFP as a measure of plasmid repair was due not only to the complex chemical structures of termini created by SSBs compared to those created by enzyme treatments, but also that base lesions or AP sites proximately arising at the strand-break termini might compromise EGFP expression. These results emphasize that radiation-induced DNA breaks are less repairable than enzymatically induced DNA breaks, which is not apparent when using conventional gel electrophoresis assays of plasmid DNA.
    Radiation research, 2021年09月01日, [査読有り]
  • 〔主要な業績〕X-ray induced luminescence spectroscopy for DNA damaging intermediates aided by a monochromatic synchrotron radiation
    Yusaku Terao; Yoshiaki Kumagai; Issei Suzuki; Takahiro Tsuchiya; Masatoshi Ukai; Akinari Yokoya; Kentaro Fujii; Yoshihiro Fukuda; Yuji Saitoh, Informa UK Limited
    International Journal of Radiation Biology, 2021年08月23日, [査読有り]
  • 〔主要な業績〕Molecular Configuration of Human Genome Neighboring Megabase-Sized Large Deletions Induced by X-Ray Irradiation.
    Eri Hirose; Keiji Suzuki; Akinari Yokoya, ラスト(シニア)オーサー, The genomic landscape neighboring large deletions including the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus on human X chromosome in 6-thioguanine-resistant mutants originating from immortalized human fibroblast cells exposed to X rays was characterized by real-time quantitative PCR (qPCR)-based analyses. Among the 13 mutant clones with large deletions extending over several Mb, including the HPRT locus, revealed by 10 conventional sequence-tagged site (STS) markers, three clones bearing the largest deletions were selected for further qPCR analysis using another 21 STS markers and 15 newly designed PCR primer pairs. The results indicated that the major deletions were in very specific regions between the 130-Mb and 140-Mb positions containing the HPRT locus on the X chromosome and, contrary to our initial expectations, additional minor deletions were distributed in a patchwork pattern. These findings strongly indicate that the complex deletion patterns in the affected chromosome are related to the radiation track structure with spatially heterogeneous energy deposition and the specific structure of the chromatin-nuclear membrane complex. The uncovered complex deletion patterns are in agreement with the idea of complex chromatin damage, which is frequently associated with carcinogenesis.
    Radiation research, 2021年06月01日, [査読有り]
  • 〔主要な業績〕Targeted Nuclear Irradiation with an X-Ray Microbeam Enhances Total JC-1 Fluorescence from Mitochondria
    Kiichi Kaminaga; Ryo Hamada; Noriko Usami; Keiji Suzuki; Akinari Yokoya, ラスト(シニア)オーサー, Several studies have demonstrated that mitochondria are critically involved in the pleiotropic manifestation of radiation effects. While conventional whole-cell irradiation compromises the function of mitochondria, the effects of subcellular targeted radiation are not yet fully understood. In this study, normal human diploid cells with cell-cycle indicators were irradiated using a synchrotron X-ray microbeam, and mitochondrial membrane potential was quantified by JC-1 over the 72-h period postirradiation. Cytoplasmic irradiation was observed to temporarily enlarge the mitochondrial area with high membrane potential, while the total mitochondrial area did not change significantly. Unexpectedly, cell-nucleus irradiation promoted a similar increase not only in the mitochondrial areas with high membrane potential, but also in those with low membrane potential, which gave rise to the apparent increase in the total mitochondrial area. Augmentation of the mitochondrial area with low membrane potential was predominantly observed among G1 cells, suggesting that nucleus irradiation during the G1 phase regulated the mitochondrial dynamics of the cytoplasm, presumably through DNA damage in the nucleus., Radiation Research Society
    Radiation Research, 2020年10月12日, [査読有り]
  • Spatially Fractionated Microbeam Analysis of Tissue-sparing Effect for Spermatogenesis
    Hisanori Fukunaga; Kiichi Kaminaga; Takuya Sato; Karl T. Butterworth; Ritsuko Watanabe; Noriko Usami; Takehiko Ogawa; Akinari Yokoya; Kevin M. Prise, Spatially fractionated radiation therapy (SFRT) has been based on the delivery of a single high-dose fraction to a large treatment area that has been divided into several smaller fields, reducing the overall toxicity and adverse effects. Complementary microbeam studies have also shown an effective tissue-sparing effect (TSE) in various tissue types and species after spatially fractionated irradiation at the microscale level; however, the underlying biological mechanism remains elusive. In the current study, using the combination of an ex vivo mouse spermatogenesis model and high-precision X-ray microbeams, we revealed the significant TSE for maintaining spermatogenesis after spatially fractionated microbeam irradiation. We used the following ratios of the irradiated to nonirradiated areas: 50:50, 150:50 and 350:50 µm-slit, where approximately 50, 75 and 87.5% of the sample was irradiated (using center-to-center distances of 100, 200 and 400 µm, respectively). We found that the 50 and 75% micro-slit irradiated testicular tissues showed an almost unadulterated TSE for spermatogenesis, whereas the 87.5% micro-slit irradiated tissues showed an incomplete TSE. This suggests that the TSE efficiency for spermatogenesis is dependent on the size of the nonirradiated spermatogonial stem cell pool in the irradiated testicular tissues. In addition, there would be a spatiotemporal limitation of stem cell migration/competition, resulting in the insufficient TSE for 87.5% micro-slit irradiated tissues. These stem cell characteristics are essential for the accurate prediction of tissue-level responses during or after SFRT, indicating the clinical potential for achieving better outcomes while preventing adverse effects., Radiation Research Society
    Radiation Research, 2020年08月19日, [査読有り]
  • 〔主要な業績〕Electronic properties of DNA-related molecules containing a bromine atom
    Misaki Hirato; Misato Onizawa; Yuji Baba; Yoshinori Haga; Kentaro Fujii; Shin-ichi Wada; Akinari Yokoya, ラスト(シニア)オーサー, Purpose: To clarify the radiosensitization mechanism masking the Auger effect of the cells possessing brominated DNA, the electronic properties of DNA-related molecules containing Br were investigated by X-ray spectroscopy and specific heat measurement. Materials and Methods: X-ray absorption near-edge structure (XANES) and X-ray photoemission spectroscopy (XPS) were used to measure the electronic properties of the nucleotides with and without Br. We determined the specific heat of 5-bromouracil crystals with thymine as a reference molecule at low temperatures of 3–48 K to calculate the microscopic state numbers. Results: Obtained XANES and XPS spectra indicated that both the lowest unoccupied molecular orbital (LUMO) and the core-levels were not affected by the Br incorporation. The state numbers of 5-bromouracil calculated from the specific heats obtained around 25 K was about 1.5 times larger than that for thymine below 20 K, although the numbers were almost the same below 5 K. Discussion: Our results suggest that the Br atom may not contribute substantially to the LUMO and core-level electronic states of the molecule, but rather to the microscopic states related to the excitation of lattice vibrations, which may be involved in valence electronic states., Informa UK Limited
    International Journal of Radiation Biology, 2020年08月12日, [査読有り]
  • マイクロビームと組織培養を用いた放射線組織生物学―保健物理学と放射線生物学の接点として
    福永久典; 横谷明徳, *Japanese, 日本保健物理学会
    保健物理, 2020年07月20日, [査読有り]
  • The Tissue-Sparing Effect of Spatially Fractionated X-rays for Maintaining Spermatogenesis: A Radiobiological Approach for the Preservation of Male Fertility after Radiotherapy.
    Hisanori Fukunaga; Kiichi Kaminaga; Takuya Sato; Ritsuko Watanabe; Takehiko Ogawa; Akinari Yokoya; Kevin M Prise, Radiotherapy can result in temporary or permanent gonadal toxicity in male cancer patients despite the high precision and accuracy of modern radiation treatment techniques. Previous radiobiological studies have shown an effective tissue-sparing response in various tissue types and species following exposure to spatially fractionated radiation. In the present study, we used an ex vivo mouse testicular tissue culture model and a conventional X-ray irradiation device to evaluate the tissue-sparing effect (TSE) of spatially fractionated X-rays for the protection of male fertility from radiotherapy-related adverse effects. We revealed a significant TSE for maintaining spermatogenesis in the ex vivo testes model following spatially fractionated X-ray irradiation. Moreover, we experimentally propose a possible mechanism by which the migration of spermatogonial cells, from the non-irradiated areas to the irradiated ones, in irradiated testicular tissue, is essential for the TSE and maintaining spermatogenesis. Therefore, our findings demonstrate that the control of TSE following spatially fractionated X-rays in the testes has a considerable potential for clinical application. Interdisciplinary research will be essential for further expanding the applicability of this method as an approach for the preservation of male fertility during or after radiotherapy.
    Journal of clinical medicine, 2020年04月11日, [査読有り]
  • 〔主要な業績〕Targeting Specific Sites in Biological Systems with Synchrotron X-Ray Microbeams for Radiobiological Studies at the Photon Factory
    Akinari Yokoya; Noriko Usami, 筆頭著者, X-ray microbeams have been used to explore radiobiological effects induced by targeting a specific site in living systems. Synchrotron radiation from the Photon Factory, Japan, with high brilliance and highly parallel directionality is a source suitable for delivering a particular beam size or shape, which can be changed according to target morphology by using a simple metal slit system (beam size from 5 μm to several millimeters). Studies have examined the non-targeted effects, called bystander cellular responses, which are thought to be fundamental mechanisms of low-dose or low-dose-rate effects in practical radiation risk research. Narrow microbeams several tens of micrometers or less in their size targeted both the cell nucleus and the cytoplasm. Our method combined with live-cell imaging techniques has challenged the traditional radiobiological dogma that DNA damage is the only major cause of radiation-induced genetic alterations and is gradually revealing the role of organelles, such as mitochondria, in these biological effects. Furthermore, three-dimensionally cultured cell systems have been used as microbeam targets to mimic organs. Combining the spatial fractionation of X-ray microbeams and a unique ex vivo testes organ culture technique revealed that the tissue-sparing effect was induced in response to the non-uniform radiation fields. Spatially fractionated X-ray beams may be a promising tool in clinical radiation therapy., MDPI AG
    Quantum Beam Science, 2020年01月09日, [査読有り]
  • 〔主要な業績〕Ab Initio Molecular Dynamics Simulations to Interpret the Molecular Fragmentation Induced in Deoxyribose by Synchrotron Soft X-Rays
    Marie-Anne Hervé du Penhoat; Anis Hamila; Marie-Pierre Gaigeot; Rodolphe Vuilleumier; Kentaro Fujii; Akinari Yokoya; Marie-Françoise Politis, It has been suggested that core ionization in DNA atoms could induce complex, irreparable damage. Synchrotron soft X-rays have been used to probe the damage induced by such events in thin films of DNA components. In a complementary approach, we investigate the fragmentation dynamics following a carbon or oxygen K-shell ionization in 2-deoxy-D-ribose (DR), a major component in the DNA chain. Core ionization of the sugars hydration layer is also studied. To that aim, we use state-of-the-art ab initio Density Functional Theory-based Molecular Dynamics (MD) simulations. The ultrafast dissociation dynamics of the core ionized molecule, prior Auger decay, is modeled for about 10 fs. We show that the core-ionization of oxygen atoms within DR or its hydration layer may induce proton transfers towards nearby molecules, before Auger decay. In a second step, we model an Auger effect occurring either at the beginning or at the end of the core–hole dynamics. Two electrons are removed from the deepest valence molecular orbitals localized on the initially core-ionized oxygen atom (O*), and this electronic state is propagated by means of Ehrenfest MD. We show an ultrafast dissociation of the DR2+ molecule C-O* bonds, which, in most cases, seems independent of the time at which Auger decay occurs., MDPI AG
    Quantum Beam Science, 2019年12月10日, [査読有り]
  • 〔主要な業績〕High-precision microbeam radiotherapy reveals testicular tissue-sparing effects for male fertility preservation
    Fukunaga Hisanori; Kaminaga Kiichi; Sato Takuya; Butterworth Karl T; Watanabe Ritsuko; Usami Noriko; Ogawa Takehiko; Yokoya Akinari; Prise Kevin M, 責任著者, Abstract
    Microbeam radiotherapy (MRT) is based on a spatial fractionation of synchrotron X-ray microbeams at the microscale level. Although the tissue-sparing effect (TSE) in response to non-uniform radiation fields was recognized more than one century ago, the TSE of MRT in the testes and its clinical importance for preventing male fertility remain to be determined. In this study, using the combination of MRT techniques and a unique ex vivo testes organ culture, we show, for the first time, the MRT-mediated TSE for the preservation of spermatogenesis. Furthermore, our high-precision microbeam analysis revealed that the survival and potential migration steps of the non-irradiated germ stem cells in the irradiated testes tissue would be needed for the effective TSE for spermatogenesis. Our findings indicated the distribution of dose irradiated in the testes at the microscale level is of clinical importance for delivering high doses of radiation to the tumor, while still preserving male fertility., Springer Science and Business Media LLC
    SCIENTIFIC REPORTS, 2019年10月01日, [査読有り]
  • VISUALIZATION OF THE DNA REPAIR PROCESS IN MAMMALIAN CELLS TRANSFECTED WITH EGFP-EXPRESSING PLASMID DNA AFTER EXPOSURE TO X-RAYS IN VITRO
    Hiroki Nakaue; Yui Obata; Kiichi Kaminaga; Nobuyoshi Akimitsu; Akinari Yokoya, ラスト(シニア)オーサー, To investigate the repair process of DNA damage induced by ionizing radiation in isolation from various types of cytoplasmic damage, we transfected X-irradiated enhanced green fluorescent protein (EGFP)-expressing plasmid DNA into non-irradiated mammalian cells using lipofectamine. The repair kinetics of the irradiated plasmids in the cells were visualized under microscopy as the EGFP fluorescence emitted by transfected cells. Using an agarose gel electrophoresis method, the yields of single- and double-strand breaks of the plasmids were also quantified. As positive control experiments, plasmid DNA with single- or double-strand breaks induced by a nicking or restriction enzyme were also transfected into the cells. The DNA repair rates for X-ray-irradiated plasmids were significantly lower than those of the enzymatically digested positive control samples. These results indicate that X-rays could induce less repairable damage than that induced by enzymes., Oxford University Press (OUP)
    Radiation Protection Dosimetry, 2019年05月01日, [査読有り]
  • NOVEL ANALYTICAL STUDY FOR REACTION INTERMEDIATES IN THE PRIMARY RADIATION INTERACTION OF DNA USING A SYNCHROTRON RADIATION-INDUCED LUMINESCENCE SPECTROSCOPY
    T Kojima; H Aihara; Y Kodashima; H Makishima; S Nakiri; S Takada; H Shimada; M Ukai; C Ozga; X Holzapfel; Ph Schmidt; C Küstner-Wetekam; H Otto; D Bloβ; A Knie; A Ehresmann; A Yokoya; K Fujii; Y Fukuda; Y Saitoh, Oxford University Press (OUP)
    Radiation Protection Dosimetry, 2019年05月01日, [査読有り]
  • STRUCTURAL ANALYSIS OF DNA REPAIR PROTEIN XRCC4 APPLYING CIRCULAR DICHROISM IN AN AQUEOUS SOLUTION
    Kai Nishikubo; Yudai Izumi; Yoshihisa Matsumoto; Kentaro Fujii; Koichi Matsuo; Akinari Yokoya, ラスト(シニア)オーサー, Oxford University Press (OUP)
    Radiation Protection Dosimetry, 2019年05月01日, [査読有り]
  • MITOCHONDRIAL MEMBRANE POTENTIAL, MORPHOLOGY AND ATP PRODUCTION IN MAMMALIAN CELLS EXPOSED TO X-RAYS
    R Hamada; K Kaminaga; K Suzuki; A Yokoya, ラスト(シニア)オーサー, Oxford University Press (OUP)
    Radiation Protection Dosimetry, 2019年05月01日, [査読有り]
  • Precision Radiotherapy and Radiation Risk Assessment: How Do We Overcome Radiogenomic Diversity?
    Fukunaga Hisanori; Yokoya Akinari; Taki Yasuyuki; Butterworth Karl T; Prise Kevin M, Tohoku University Medical Press
    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 2019年04月, [査読有り]
  • XANES Spectral Changes of Hydrated Deoxyribose Induced by K-Shell Ionization of Oxygen
    Fujii Kentaro; Yokoya Akinari
    13TH INTERNATIONAL CONFERENCE ON SYNCHROTRON RADIATION INSTRUMENTATION (SRI2018), 2019年, [査読有り]
  • 〔主要な業績〕Substituent effect on the yield of unpaired electrons in DNA bases studied by electron paramagnetic resonance
    Oka Toshitaka; Yokoya Akinari; Fujii Kentaro; Kino Yasushi; Sekine Tsutomu, The physicochemical processes underlying the radiation sensitization of DNA by the K-shell photoabsorption of nitrogen and oxygen atoms are unclear. Accordingly, we evaluated electron paramagnetic resonance spectra of thin films of pyrimidine bases. By altering the substituents of the pyrimidine ring, we found a substituent effect on the yield of unpaired electrons induced by photo-absorption. The yield of the unpaired electrons of the DNA-base containing amino groups increased by the donation of electrons, and the yield of halogenated DNA-bases decreased by the withdrawal of electrons. These different physicochemical processes might affect DNA bases, leading to differences in DNA modification. Published by AIP Publishing., AMER INST PHYSICS
    APPLIED PHYSICS LETTERS, 2018年12月10日, [査読有り]
  • 〔主要な業績〕Application of an Ex Vivo Tissue Model to Investigate Radiobiological Effects on Spermatogenesis
    Hisanori Fukunaga; Kiichi Kaminaga; Takuya Sato; Noriko Usami; Ritsuko Watanabe; Karl T. Butterworth; Takehiko Ogawa; Akinari Yokoya; Kevin M. Prise, 責任著者, The formation of sperm by the testes through the process of spermatogenesis is highly radiosensitive and can be affected by environmental, occupational and therapeutic radiation exposures. In this study, we applied an ex vivo mouse testis organ culture as an experimental model of spermatogenesis to investigate the radiobiological effects and to demonstrate its feasibility as a tool to determine response to complex, modulated radiation fields. This model uses Acr-GFP transgenic mice, which express the marker green fluorescent proteins specific for meiosis to allow observation of functional changes in real-time that can be used to analyze radiation-induced changes in the process of spermatogenesis. Our results showed that the model can accurately reproduce radiation-induced male germ cell toxicity, such as temporary infertility and permanent sterility. Furthermore, using a monochromatic X-ray microbeam, we applied this model to investigate the effects of heterogeneous radiation fields on testis tissue ex vivo. Our model represents a unique application in the field, which offers significant potential for gaining further mechanistic insight into radiation effects on the process of spermatogenesis., Radiation Research Society
    Radiation Research, 2018年06月01日, [査読有り]
  • 〔主要な業績〕Roles of Hydration for Inducing Decomposition of 2-Deoxy-d-ribose by Ionization of Oxygen K-Shell Electrons
    Kentaro Fujii; Yudai Izumi; Ayumi Narita; Krishna Kamol Ghose; Pablo López-Tarifa; Alain Touati; Riccardo Spezia; Rodolphe Vuilleumier; Marie-Pierre Gaigeot; Marie-Françoise Politis; Marie-Anne Hervé Du Penhoat; Akinari Yokoya, To experimentally investigate the role of hydration in the initial process of the decomposition of 2-deoxy-d-ribose (dR), which is a major component of the DNA backbone, we used mass spectrometry to monitor the ions desorbing from hydrated dR films exposed to monochromatic soft X rays (560 eV). The X-ray photons preferentially ionize the K-shell electrons of the oxygen atoms in DNA. Hydrated dR samples were prepared under vacuum by exposing a cooled (~150 K) dR film deposited on a Si substrate to water vapor. Using a quadrupole mass spectrometer, we observed the desorption of ions such as H+, CHx+, C2Hx+, CHxO+, C3Hx+ and C2HxO+ (x = 1, 2, 3 and 4). In addition, the desorption of H2O+ or H3O+ was observed in the mass spectra of hydrated dR films. Except for H+, the yields of these ions decreased when one layer of water molecules was deposited onto the film. These ions are produced by C-C or C-O bond scission. This result suggests that the water molecules act as a quencher, suppressing Coulomb repulsion and thus the extensive molecular decomposition of dR. Ab initio molecular dynamics simulations were performed to rationalize the fragments observed in the experiments. The results of the dynamical process of a hydrated dR molecule after oxygen K-ionization revealed elongation of a C-O bond of dR and the O-H bonds of both dR and water molecules prior to the Auger process, resulting in the ejection of H+ ions. These results strongly suggest that the very early process contributes to reducing the dR fragmentation, producing the H3O+ and H+ detected from the hydrated dR films. These desorbed ions may be involved in the induction of other types of damage, such as oxidatively generated base lesions, concomitantly produced with a strand break when produced in DNA., Radiation Research Society
    Radiation Research, 2018年03月01日, [査読有り]
  • 〔主要な業績〕Circular dichroism spectroscopic study on structural alterations of histones induced by post-translational modifications in DNA damage responses: lysine-9 methylation of H3
    Yudai Izumi; Koichi Matsuo; Kentaro Fujii; Akinari Yokoya; Masaki Taniguchi; Hirofumi Namatame, Oxford University Press (OUP)
    Journal of Radiation Research, 2018年03月01日, [査読有り]
  • 放射線物理化学過程に関する最近の進展(後編)
    甲斐健師; 横谷明徳; 藤井健太郎; 渡邊立子
    放射線化学(Web), 2018年
  • 〔主要な業績〕A significant role of non-thermal equilibrated electrons in the formation of deleterious complex DNA damage
    Takeshi Kai; Akinari Yokoya; Masatoshi Ukai; Kentaro Fujii; Tomohiro Toigawa; Ritsuko Watanabe, Although most of the radiation damage to genomic DNA could be rendered harmless using repair enzymes in a living cell, a certain fraction of the damage is persistent resulting in serious genetic effects, such as mutation induction. In order to understand the mechanisms of the deleterious DNA damage formation in terms of its earliest physical stage at the radiation track end, dynamics of low energy electrons and their thermalization processes around DNA molecules were investigated using a dynamic Monte Carlo code. The primary incident (1 keV) electrons multiply collide within 1 nm (equivalent to three DNA-base-pairs, 3bp) and generate secondary electrons which show non-Gaussian and non-thermal equilibrium distributions within 300 fs. On the other hand, the secondary electrons are mainly distributed within approximately 10 nm from their parent cations although approximately 5% of the electrons are localized within 1 nm of the cations owing to the interaction of their Coulombic fields. The mean electron energy is 0.7 eV
    however, more than 10% of the electrons fall into a much lower-energy region than 0.1 eV at 300 fs. These results indicate that pre-hydrated electrons are formed from the extremely decelerated electrons over a few nm from the cations. DNA damage sites comprising multiple nucleobase lesions or single strand breaks can therefore be formed by multiple collisions of these electrons within 3bp. This multiple damage site is hardly processed by base excision repair enzymes. However, pre-hydrated electrons can also be produced resulting in an additional base lesion (or a strand break) more than 3bp away from the multi-damage site. These damage sites may be finally converted into a double strand break (DSB) when base excision enzymes process the additional base lesions. This DSB includes another base lesion(s) at their termini, and may introduce miss-rejoining by DSB repair enzymes, and hence may result in biological effects such as mutation in surviving cells., Royal Society of Chemistry
    Physical Chemistry Chemical Physics, 2018年, [査読有り]
  • Radiobiological Implications of Fukushima Nuclear Accident for Personalized Medical Approach
    Hisanori Fukunaga; Akinari Yokoya; Yasuyuki Taki; Kevin M. Prise, On March 11, 2011, a devastating earthquake and subsequent tsunami caused serious damage to areas of the Pacific coast in Fukushima prefecture and prompted fears among the residents about a possible meltdown of the Fukushima Daiichi Nuclear Power Plant reactors. As of 2017, over six years have passed since the Fukushima nuclear crisis and yet the full ramifications of the biological exposures to this accidental release of radioactive substances remain unclear. Furthermore, although several genetic studies have determined that the variation in radiation sensitivity among different individuals is wider than expected, personalized medical approaches for Fukushima victims have seemed to be insufficient. In this commentary, we discuss radiobiological issues arising from low-dose radiation exposure, from the cell based to the population level. We also introduce the scientific utility of the Integrative Japanese Genome Variation Database (iJGVD), an online database released by the Tohoku Medical Megabank Organization, Tohoku University that covered the whole genome sequences of 2,049 healthy individuals in the northeastern part of Japan in 2016. Here we propose a personalized radiation risk assessment and medical approach, which considers the genetic variation of radiation sensitivity among individuals, for next step developments in radiological protection., TOHOKU UNIV MEDICAL PRESS
    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 2017年05月, [査読有り]
  • 抗酸化物質エダラボンによる活性酸素除去およびDNA酸化損傷の化学的修復
    端邦樹; LIN Mingzhang; 横谷明徳; 藤井健太郎; 山下真一; 室屋裕佐; 勝村庸介
    放射線化学(Web), 2017年04月, [査読有り]
  • Efficiency of radiation-induced base lesion excision and the order of enzymatic treatment
    Iyo Shiraishi; Naoya Shikazono; Masao Suzuki; Kentaro Fujii; Akinari Yokoya, 責任著者, Purpose: To clarify whether initial base excision repair processes at clustered DNA damage sites comprising multiple base lesions affect subsequent excision processes via the formation of additional strand breaks by glycosylase and apurinic/apyrimidinic (AP) endonuclease base excision enzymes.Materials and methods: Plasmid DNA (pUC18) as a model DNA molecule was exposed to high-linear-energy-transfer (LET) ionizing radiation (He(2+)or C(6+)ions) or low-LET ionizing radiation (X-rays) under various conditions to produce varied radical-scavenging effects. pUC18 was then treated sequentially or simultaneously with two bacterial base excision enzymes (glycosylases), namely, endonuclease III and formamidopyrimidine-DNA glycosylase, which convert pyrimidine (or abasic [AP] site) and purine (or AP site) lesions to single-strand breaks (SSB), respectively. Yields of additional SSB or double-strand breaks (DSB) as digestion products were examined after changing the order of enzymatic treatment.Results: There were few differences among the enzymatic treatments, indicating that treatment order did not affect the final yields of additional SSB or DSB formed by glycosylase activity. This suggests that of the total damage, the fraction of clustered damage sites with a persistent base lesion dependent on the order of glycosylase treatment was insignificant if present.Conclusion: Base lesion clusters induced by high- or low-LET radiation appear three or more base pairs apart, and are promptly converted to a DSB by glycosylase, regardless of the order of enzymatic treatment., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2017年03月, [査読有り]
  • 高エネルギー電子線により水中で生成された2次電子の動的挙動
    甲斐健師; 横谷明徳; 藤井健太郎; 渡邊立子
    陽電子科学, 2017年
  • 〔主要な業績〕DNA damage response induces structural alterations in histone H3-H4
    Yudai Izumi; Kentaro Fujii; Satoshi Yamamoto; Koichi Matsuo; Hirofumi Namatame; Masaki Taniguchi; Akinari Yokoya, Synchrotron-radiation circular-dichroism spectroscopy was used to reveal that the DNA damage response induces a decrement of alpha-helix and an increment of beta-strand contents of histone H3-H4 extracted from X-ray-irradiated human HeLa cells. The trend of the structural alteration was qualitatively opposite to that of our previously reported results for histone H2A-H2B. These results strongly suggest that histones share roles in DNA damage responses, particularly in DNA repair processes and chromatin remodeling, via a specific structural alteration of each histone., OXFORD UNIV PRESS
    JOURNAL OF RADIATION RESEARCH, 2017年01月, [査読有り]
  • 〔主要な業績〕Photon-induced Auger effect in biological systems: a review
    Akinari Yokoya; Takashi Ito, 筆頭著者, Purpose: In this paper, we review interesting findings reported in the studies of the biological effects induced by inner-shell ionization with the aim of interpreting them from a mechanistic viewpoint, in particular, of the Auger effect of atoms on different biological systems.
    Materials and methods: More than 70 published papers are cited on the Auger effects ranging from DNA-related elements (carbon, nitrogen, oxygen and phosphorus) to mammalian cells. Externally administrated bromine, iodine, and platinum have also been cited for the present endeavor. Those significant works all needed a highly monochromatized X-rays from brilliant synchrotron light sources.
    Results: We have assembled a coherent view on the inner-shell effects of the Auger process that contrasts to the overall effects with the outer-shell ionization processes.
    Conclusion: Some of these studies have reported that the Auger effect significantly enhances biological effects as compared with irradiation at below K-ionization energy. The Auger-specific molecular degradation mode of DNA, involving extensive fragmentation of the deoxypentose moiety, has also been revealed. We conclude that the selectively localized effect on the specified atoms through inner-shell ionization followed by the Auger process should have a definite impact on the current radiation effect studies, which are largely based on non-selective outer-shell ionizations., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2017年, [査読有り]
  • Low-dose radiation-induced risk in spermatogenesis
    Hisanori Fukunaga; Karl T. Butterworth; Akinari Yokoya; Takehiko Ogawa; Kevin M. Prise, Purpose: To discuss low-dose radiation-induced risks to male fertility focusing on potential mechanisms of low-dose radiation-induced damage on spermatogenesis, epidemiological studies of environmental radiation effects on sperm parameters and transgenerational effects following exposure of spermatogonial stem cells (SSCs).Background: Spermatogenesis produces mature male gametes, spermatozoa, which fertilize their counterpart female gametes, oocytes. The robust maintenance system of spermatogenesis is essential for genomic conservation; however, male fertility can be readily impacted by exposure to environmental, chemical and physical factors including ionizing radiation. The mammalian testes are known to be radiosensitive yet the underlying molecular mechanisms of low-dose radiation-induced risks for spermatogenesis remain unclear. Furthermore, evidence characterizing transgenerational effects following exposure of SSCs remain controversial.Conclusions: Current concerns over the possible effects of low-dose radiation exposure on spermatogenesis requires further elucidation that may be resolved comparing and integrating observed experimental and epidemiological data., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2017年, [査読有り]
  • The 8th Auger Symposium: Preface
    Akinari Yokoya, 筆頭著者, TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2016年11月, [査読有り], [招待有り]
  • Enhancement of DNA double-strand break induction and cell killing by K-shell absorption of phosphorus in human cell lines
    Masanori Tomita; Munetoshi Maeda; Noriko Usami; Akinari Yokoya; Ritsuko Watanabe; Katsumi Kobayashi, Purpose: To investigate an enhancement of DNA double-strand break (DSB) induction and cell killing effect by K-shell ionization of phosphorus atoms and Auger electrons on human cell lines.Materials and methods: Induction of DSB, DNA damage responses, cell cycle distributions, and cell killing effects were investigated after exposures of the cells with monochromatic synchrotron radiation soft X-rays of 2153 and 2147eV, which were the resonance peak and off peak, respectively, of the K-shell photoabsorption of phosphorus.Results: Higher biological effects in the cells irradiated with soft X-rays at 2153eV than at 2147eV were observed in (i) the efficiency of 53BP1/-H2AX co-localized foci formation per dose and residual number of foci, (ii) prolonged phosphorylation levels of DSB repair and/or cell cycle checkpoint related proteins and G2 arrest, (iii) the cell killing effects at the 10% survival level of normal human fibroblasts, HeLa cells, and human glioblastoma M059K cells (1.2-1.5 times higher) and that of human ataxia telangiectasia mutated (ATM)-defective cells and glioblastoma DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-defective cells (1.2 times).Conclusion: The yield of DSB and partly less-reparable complex DNA damage induction in human cells was enhanced by K-shell photoabsorption of phosphorus and low-energy Auger electrons., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2016年11月, [査読有り]
  • Deceleration processes of secondary electrons produced by a high-energy Auger electron in a biological context
    Takeshi Kai; Akinari Yokoya; Masatoshi Ukai; Kentaro Fujii; Ritsuko Watanabe, Purpose: To simulate the deceleration processes of secondary electrons produced by a high-energy Auger electron in water, and particularly to focus on the spatial and temporal distributions of the secondary electron and the collision events (e.g. ionization, electronic excitation, and dissociative electron attachment) that are involved in the multiplication of lesions at sites of DNA damage.Materials and methods: We developed a dynamic Monte Carlo code that considers the Coulombic force between an ejected electron and its parent cation produced by the Auger electron in water. Thus our code can simulate some return electrons to the parent cations. Using the code, we calculated to within the order of femtoseconds the temporal evolution of collision events, the mean energy, and the mean traveling distance (including its spatial probability distribution) of the electron at an ejected energy of 20eV.Results: Some of the decelerating electrons in water in the Coulombic field were attracted to the ionized atoms (cations) by the Coulombic force within hundreds of femtoseconds, although the force did not significantly enhance the number of ionization, electronic excitation, and dissociative electron attachment collision events leading to water radiolysis.Conclusions: The secondary electrons are decelerated in water by the Coulombic force and recombined to the ionized atoms (cations). Furthermore, the some return electrons might be prehydrated in water layer near the parent cation in DNA if the electrons might be emitted from the DNA. The prehydrated electron originated from the return electron might play a significant role in inducing DNA damage., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2016年11月, [査読有り]
  • Cell cycle tracking for irradiated and unirradiated bystander cells in a single colony with exposure to a soft X-ray microbeam
    Kiichi Kaminaga; Miho Noguchi; Ayumi Narita; Yuya Hattori; Noriko Usami; Akinari Yokoya, 責任著者, Purpose: To establish a new experimental technique to explore the photoelectric and subsequent Auger effects on the cell cycles of soft X-ray microbeam-irradiated cells and unirradiated bystander cells in a single colony.Materials and methods: Several cells located in the center of a microcolony of HeLa-Fucci cells consisting of 20-80 cells were irradiated with soft X-ray (5.35keV) microbeam using synchrotron radiation as a light source. All cells in the colony were tracked for 72h by time-lapse microscopy imaging. Cell cycle progression, division, and death of each cell in the movies obtained were analyzed by pedigree assay. The number of cell divisions in the microcolony was also determined.Results: The fates of these cells were clarified by tracking both irradiated and unirradiated bystander cells. Irradiated cells showed significant cell cycle retardation, explosive cell death, or cell fusion after a few divisions. These serious effects were also observed in 15 and 26% of the bystander cells for 10 and 20Gy irradiation, respectively, and frequently appeared in at least two daughter or granddaughter cells from a single-parent cell.Conclusions: We successfully tracked the fates of microbeam-irradiated cells and unirradiated bystander cells with live cell recordings, which have revealed the dynamics of soft X-ray irradiated and unirradiated bystander cells for the first time. Notably, cell deaths or cell cycle arrests frequently arose in closely related cells. These details would not have been revealed by a conventional immunostaining imaging method. Our approach promises to reveal the dynamic cellular effects of soft X-ray microbeam irradiation and subsequent Auger processes from various endpoints in future studies., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2016年11月, [査読有り]
  • Now Is the Time to Consider Personalized Effective Dose
    Hisanori Fukunaga; Akinari Yokoya; Yasuyuki Taki, ELSEVIER SCIENCE INC
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2016年10月, [査読有り]
  • 〔主要な業績〕Dynamic Behavior of Secondary Electrons in Liquid Water at the Earliest Stage upon Irradiation: Implications for DNA Damage Localization Mechanism
    Takeshi Kai; Akinari Yokoya; Masatoshi Ukai; Kentaro Fujii; Ritsuko Watanabe, To clarify the formation of radiation damage in DNA, the dynamic behavior of low-energy secondary electrons produced by ionizing radiation in water was studied by using a dynamic Monte Carlo code that considers the Coulombic force between electrons and their parent cations. The calculated time evolution of the mean energy, total track length, and mean traveling distance of the electrons indicated that the prehydration of the electrons occurs competitively with thermalization on a time scale of hundreds of femtoseconds. The decelerating electrons are gradually attracted to their parent cations by Coulombic force within hundreds of femtoseconds, and finally about 12.6% electrons are distributed within 2 nm of the cations. The collision fraction for ionization and electronic excitation within 1 nm of the cation was estimated to be about 40%. If these electrons are decelerated in a living cell, they may cause highly localized lesions around a cation in a DNA molecule through additional dissociative electron transfer (DET) as well as ionization and electronic excitation (EXC), possibly resulting in cell death or mutation., AMER CHEMICAL SOC
    JOURNAL OF PHYSICAL CHEMISTRY A, 2016年10月, [査読有り]
  • 〔主要な業績〕Structure Change from beta-Strand and Turn to alpha-Helix in Histone H2A-H2B Induced by DNA Damage Response
    Yudai Izumi; Kentaro Fujii; Frank Wien; Chantal Houee-Levin; Sandrine Lacombe; Daniela Salado-Leza; Erika Porcel; Rawand Masoud; Satoshi Yamamoto; Matthieu Refregiers; Marie-Anne Herve du Penhoat; Akinari Yokoya, Using synchrotron radiation-based circular dichroism spectroscopy, we found that the DNA damage response induces an increase of alpha-helix structure and a decrease of beta-strand and turn structures in histone H2A-H2B extracted from x-irradiated human HeLa cells. The structural alterations correspond to the assumption that an average of eight amino acid residues form new alpha-helix structures at 310 K. We propose the structural transition from beta-strand and turn structures to an a-helix structure in H2A-H2B as a novel, to our knowledge, process involved in the DNA damage response., CELL PRESS
    BIOPHYSICAL JOURNAL, 2016年07月, [査読有り]
  • 紫外円二色性スペクトルを用いたタンパク質構造研究
    泉雄大; 山本悟史; 藤井健太郎; 横谷明徳; 横谷明徳, ラスト(シニア)オーサー
    放射線生物研究, 2016年03月, [査読有り], [招待有り]
  • 放射線物理化学過程に関する最近の進展(前編)
    甲斐健師; 横谷明徳; 藤井健太郎; 渡邊立子
    放射線化学(Web), 2016年
  • 放射線物理化学過程に関する最近の進展(中編)
    甲斐健師; 横谷明徳; 藤井健太郎; 渡邊立子
    放射線化学(Web), 2016年
  • 水溶液環境下における生体分子放射線損傷の分光研究
    島田紘行; 横谷明徳; 鵜飼正敏
    日本物理学会誌, 2016年, [査読有り], [招待有り]
  • 〔主要な業績〕Low-dose radiation risk and individual variation in radiation sensitivity in Fukushima
    Hisanori Fukunaga; Akinari Yokoya, OXFORD UNIV PRESS
    JOURNAL OF RADIATION RESEARCH, 2016年01月, [査読有り]
  • 〔主要な業績〕Cellular automaton-based model for radiation-induced bystander effects
    Yuya Hattori; Akinari Yokoya; Ritsuko Watanabe, Background: The radiation-induced bystander effect is a biological response observed in non-irradiated cells surrounding an irradiated cell. The bystander effect is known to be induced by two intercellular signaling pathways, the medium-mediated pathway (MDP) and the gap junctional pathway (GJP). To investigate the relative contribution of each signaling pathway, we have developed a mathematical model of the cellular response through these two pathways, with a particular focus on cell-cycle modification.
    Methods: The model is based on a cellular automaton and consists of four components: (1) irradiation, (2) generation and diffusion of intercellular signals, (3) induction of DNA double-strand breaks (DSBs), and (4) cell-cycle modification or cell death. The intercellular signals are generated in and released from irradiated cells. The signals through the MDP and the GJP are modeled independently based on diffusion equations. The irradiation and both signals raise the number of DSBs, which determines transitions of cellular states, such as cell-cycle arrest or cell death.
    Results: Our model reproduced fairly well previously reported experimental data on the number of DSBs and cell survival curves. We examined how radiation dose and intercellular signaling dynamically affect the cell cycle. The analysis of model dynamics for the bystander cells revealed that the number of arrested cells did not increase linearly with dose. Arrested cells were more efficiently accumulated by the GJP than by the MDP.
    Conclusions: We present here a mathematical model that integrates various bystander responses, such as MDP and GJP signaling, DSB induction, cell-cycle arrest, and cell death. Because it simulates spatial and temporal conditions of irradiation and cellular characteristics, our model will be a powerful tool to predict dynamical radiobiological responses of a cellular population in which irradiated and non-irradiated cells co-exist., BIOMED CENTRAL LTD
    BMC SYSTEMS BIOLOGY, 2015年12月, [査読有り]
  • 〔主要な業績〕Secondary Structure Alterations of Histones H2A and H2B in X-Irradiated Human Cancer Cells: Altered Histones Persist in Cells for at Least 24 Hours
    Yudai Izumi; Satoshi Yamamoto; Kentaro Fujii; Akinari Yokoya, We measured and compared the circular dichroism (CD) spectra and secondary structures of histone proteins H2A, H2B and their variants extracted from X-irradiated and unirradiated human HeLa cells. Compared to unirradiated cells, a relative increase in alpha-helix structure and decrease in other secondary structures was observed in X-irradiated cells. These structural alterations persisted for at least 24 h, which is substantially longer than the 2 h generally known to be required for DNA double-strand break repair. (C) 2015 by Radiation Research Society, RADIATION RESEARCH SOC
    RADIATION RESEARCH, 2015年11月, [査読有り]
  • Thermal equilibrium and prehydration processes of electrons injected into liquid water calculated by dynamic Monte Carlo method
    Takeshi Kai; Akinari Yokoya; Masatoshi Ukai; Kentaro Fujii; Ritsuko Watanabe, The thermalization length and spatial distribution of electrons in liquid water were simulated for initial electron energies ranging from 0.1 eV to 100 keV using a dynamic Monte Carlo code. The results showed that electrons were decelerated for thermalization over a longer time period than was previously predicted. This long thermalization time significantly contributed to the series of processes from initial ionization to hydration. We further studied the particular deceleration process of electrons at an incident energy of 1 eV, focusing on the temporal evolution of total track length, mean traveling distance, and energy distributions of decelerating electrons. The initial prehydration time and thermalization periods were estimated to be approximately 50 and 220 fs, respectively, indicating that the initial prehydration began before or contemporaneously with the thermal equilibrium. Based on these results, the prehydrated electrons were suggested to play an important role during multiple DNA damage induction. (C) 2015 Elsevier Ltd. All rights reserved., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2015年10月, [査読有り]
  • Real-time observation of irradiated HeLa-cell modified by fluorescent ubiquitination-based cell-cycle indicator using synchrotron X-ray microbeam
    A. Narita; K. Kaminaga; A. Yokoya; M. Noguchi; K. Kobayashi; N. Usami; K. Fujii, Fluorescent ubiquitination-based cell-cycle indicator (FUCCI) human cancer (HeLa) cells (red indicates G1; green, S/G2) were exposed to a synchrotron X-ray microbeam. Cells in either G1 or S/G2 were irradiated selectively according to their colour in the same microscopic field. Time-lapse micrographs of the irradiated cells were acquired for 24 h after irradiation. For fluorescent immunostaining, phosphorylated histone proteins (gamma-H2AX) indicated the induction of DNA double-strand breaks. The cell cycle was arrested by irradiation at S/G2. In contrast, cells irradiated at G1 progressed to S/G2. The foci were induced in cells irradiated at both G1 and S/G2, suggesting that the G1-S (or S) checkpoint pathway does not function in HeLa cells due to the fact that the cells are functionally p53 deficient, even though X-ray microbeam irradiation significantly induces double-strand breaks. These results demonstrate that single FUCCI cell exposure and live cell imaging are powerful methods for studying the effects of radiation on the cell cycle., OXFORD UNIV PRESS
    RADIATION PROTECTION DOSIMETRY, 2015年09月, [査読有り]
  • Visualisation of cell cycle modifications by X-ray irradiation of single HeLa cells using fluorescent ubiquitination-based cell cycle indicators
    K. Kaminaga; M. Noguchi; A. Narita; Y. Sakamoto; Y. Kanari; A. Yokoya, 責任著者, To explore the effects of X-ray irradiation on mammalian cell cycle dynamics, single cells using the fluorescent ubiquitination-based cell cycle indicator (Fucci) technique were tracked. HeLa cells expressing Fucci were used to visualise cell cycle modifications induced by irradiation. After cultured HeLa-Fucci cells were exposed to 5 Gy X-rays, fluorescent cell images were captured every 20 min for 48 h using a fluorescent microscope. Time dependence of the fluorescence intensity of S/G2 cells was analysed to examine the cell cycle dynamics of irradiated and non-irradiated control cells. The results showed that irradiated cells could be divided into two populations: one with similar cell cycle dynamics to that of non-irradiated cells, and another displaying a prolonged G2 phase. Based on these findings, it is proposed in this article that an underlying switch mechanism is involved in cell cycle regulation and the G2/M checkpoint of HeLa cells., OXFORD UNIV PRESS
    RADIATION PROTECTION DOSIMETRY, 2015年09月, [査読有り]
  • A mathematical model of radiation-induced responses in a cellular population including cell-to-cell communications
    Yuya Hattori; Michiyo Suzuki; Tomoo Funayama; Yasuhiko Kobayashi; Akinari Yokoya; Ritsuko Watanabe, Cell-to-cell communication is an important factor for understanding the mechanisms of radiation-induced responses such as bystander effects. In this study, a new mathematical model of intercellular signalling between individual cells in a cellular population is proposed. The authors considered two types of transmission of signals: via culture medium and via gap junction. They focus on the effects that radiation and intercellular signalling have on cell-cycle modification. The cell cycle is represented as a virtual clock that includes several checkpoint pathways within a cyclic process. They also develop a grid model and set up diffusion equations to model the propagation of signals to and from spatially located cells. The authors have also considered the role that DNA damage plays in the cycle of cells which can progress through the cell cycle or stop at the G1, S, G2 or M-phase checkpoints. Results of testing show that the proposed model can simulate intercellular signalling and cell-cycle progression in individual cells during and after irradiation., OXFORD UNIV PRESS
    RADIATION PROTECTION DOSIMETRY, 2015年09月, [査読有り]
  • LIVE-CELL IMAGING STUDY OF MITOCHONDRIAL MORPHOLOGY IN MAMMALIAN CELLS EXPOSED TO X-RAYS
    M. Noguchi; Y. Kanari; A. Yokoya; A. Narita; K. Fujii, Morphological changes in mitochondria induced by X-irradiation in normal murine mammary gland cells were studied with a live-cell microscopic imaging technique. Mitochondria were visualised by staining with a specific fluorescent probe in the cells, which express fluorescent ubiquitination-based cell-cycle indicator 2 (Fucci2) probes to visualise cell cycle. In unirradiated cells, the number of cells with fragmented mitochondria was about 20 % of the total cells through observation period (96 h). In irradiated cells, the population with fragmented mitochondria significantly increased depending on the absorbed dose. Particularly, for 8 Gy irradiation, the accumulation of fragmentation persists even in the cells whose cell cycle came to a stand (80 % in G1 (G0-like) phase). The fraction reached to a maximum at 96 h after irradiation. The kinetics of the fraction with fragmented mitochondria was similar to that for cells in S/G2/M phase (20 %) through the observation period (120 h). The evidences show that, in irradiated cells, some signals are continually released from a nucleus or cytoplasm even in the G0-like cells to operate some sort of protein machineries involved in mitochondrial fission. It is inferred that this delayed mitochondrial fragmentation is strongly related to their dysfunction, and hence might modulate radiobiological effects such as mutation or cell death., OXFORD UNIV PRESS
    RADIATION PROTECTION DOSIMETRY, 2015年09月, [査読有り]
  • 〔主要な業績〕Nitrogen K-edge x-ray absorption near edge structure of pyrimidine-containing nucleotides in aqueous solution
    Hiroyuki Shimada; Hirotake Minami; Naoto Okuizumi; Ichiro Sakuma; Masatoshi Ukai; Kentaro Fujii; Akinari Yokoya; Yoshihiro Fukuda; Yuji Saitoh, X-ray absorption near edge structure (XANES) was measured at energies around the N K-edge of the pyrimidine-containing nucleotides, cytidine 5'-monophosphate (CMP), 2'-deoxythymidine 5'-monophosphate (dTMP), and uridine 5'-monophosphate (UMP), in aqueous solutions and in dried films under various pH conditions. The features of resonant excitations below the N K-edge in the XANES spectra for CMP, dTMP, and UMP changed depending on the pH of the solutions. The spectral change thus observed is systematically explained by the chemical shift of the core-levels of N atoms in the nucleobase moieties caused by structural changes due to protonation or deprotonation at different proton concentrations. This interpretation is supported by the results of theoretical calculations using density functional theory for the corresponding nucleobases in the neutral and protonated or deprotonated forms. (C) 2015 AIP Publishing LLC., AMER INST PHYSICS
    JOURNAL OF CHEMICAL PHYSICS, 2015年05月, [査読有り]
  • Cross sections, stopping powers, and energy loss rates for rotational and phonon excitation processes in liquid water by electron impact
    Takeshi Kai; Akinari Yokoya; Masatoshi Ukai; Ritsuko Watanabe, We calculated cross sections, stopping powers, and energy loss rates for rotational and phonon-mode excitations caused by the impact of an electron in an energy region from 0.1 meV to 100 eV injected into liquid water. The spatial distribution of the decelerated electron depends on these cross sections. We performed calculations assuming an optical approximation with the dielectric functions that are experimentally reported in the literature. We observed that the cross sections lie below 1 x 10(-16) cm(2) over the considered energy region. The values for rotational excitation processes in the liquid phase are less by three orders of magnitude than those in the gas phase because of the screening effect of neighboring water molecules on the interaction between the incident electron and water molecules. These results suggest that the cross sections in the liquid phase are significantly different from those in the gas phase. The values for phonon-mode excitations in the liquid phase are close to those reported for amorphous ice. Furthermore, we observed that the stopping power shows a maximum around 200 meV, and the energy loss rates, which are derived from the stopping power, depend significantly on the electron energy, particularly below 1 eV. The values obtained here will allow us to precisely estimate the decelerating process of an electron in liquid water to predict radiation effects such as chemical processes in water radiolysis or biomolecular damage induction strongly involved in low energy electron processes. (C) 2014 Elsevier Ltd. All rights reserved., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2015年03月, [査読有り]
  • 〔主要な業績〕Investigation of the fragmentation of core-ionised deoxyribose: a study as a function of the tautomeric form
    Marie-Anne Herve du Penhoat; Krishna Kamol Ghose; Marie-Pierre Gaigeot; Rodolphe Vuilleumier; Kentaro Fujii; Akinari Yokoya; Marie-Francoise Politis, We have investigated the gas phase fragmentation dynamics following the core ionisation of 2-deoxy-Dribose (dR), a major component in the DNA chain. To that aim, we use state-of-the-art ab initio Density Functional Theory-based Molecular Dynamics simulations. The ultrafast dissociation dynamics of the core-ionised biomolecule, prior Auger decay, is first modelled for 10 fs to generate initial configurations (atomic positions and velocities) for the subsequent dynamics of the doubly ionised biomolecule in the ground state. The furanose, linear and pyranose conformations of dR were investigated. We show that fragmentation is relatively independent of the atom struck or of the duration of the core vacancy, but depends rather critically on the molecular orbital removed following Auger decay., ROYAL SOC CHEMISTRY
    PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 2015年, [査読有り]
  • 〔主要な業績〕Live-cell imaging study of radiation effect on cell cycles of three-dimensional cultured cells exposed to synchrotron soft X-ray microbeam               
    坂本由佳; 神長輝一; 嘉成由紀子; 宇佐美徳子; 野口実穂; 横谷明徳, 責任著者
    乳癌基礎研究, 2015年, [査読有り]
  • 〔主要な業績〕Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA
    Kuniki Hata; Ayumi Urushibara; Shinichi Yamashita; Mingzhang Lin; Yusa Muroya; Naoya Shikazono; Akinari Yokoya; Haiying Fu; Yosuke Katsumura, Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 x 10(8) dm(3) mol(-1) s(-1) and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10-1000 mu mol dm(-3)) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid., OXFORD UNIV PRESS
    JOURNAL OF RADIATION RESEARCH, 2015年01月, [査読有り]
  • Dynamics of low-energy electrons in liquid water with consideration of Coulomb interaction with positively charged water molecules induced by electron collision
    Takeshi Kai; Akinari Yokoya; Masatoshi Ukai; Kentaro Fujii; Mariko Higuchi; Ritsuko Watanabe, To explain the electron energy relaxation process in water, we performed dynamical calculations of electrons in water using a simulation code developed in this study to calculate mean diffusion distances and mean energies of incident and secondary electrons released by the impact of the incident electron, as well as spatial probability-distribution of the secondary electrons. In addition to the following molecular processes of water: ionization: electronic, vibrational, and rotational excitation by electron impact; dissociative electron attachment; and elastic electron scattering, which were basic parameters used by Monte Carlo simulation, we newly took into account Coulomb interactions between electrons and positively ionized water molecules to calculate classical electron trajectories. We found that the Coulomb interactions enhance the number of collisions for the vibrational and rotational excitation processes at the incident 500 eV electron energy. The secondary electrons diffuse to an average of 3 nm from their original position, resulting much different spatial probability-distribution of those electrons in comparison to those previously reported. We also found that approximately 20% of the secondary electrons were returned to the parent ions within 100 fs. By the electron re-capturing to either bonding or antibionding orbital, the molecules might be converted to some electronic excitation states. We suggest that the spatial probability-distribution of electrons, taken into account the re-capturing process, should be essential for detailed analysis of following chemical process arising in nanometer scales, such as biomolecular damage caused by radiation. (C) 2014 Elsevier Ltd. All rights reserved., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2014年09月, [査読有り]
  • Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution
    Hiroyuki Shimada; Taishi Fukao; Hirotake Minami; Masatoshi Ukai; Kentaro Fujii; Akinari Yokoya; Yoshihiro Fukuda; Yuji Saitoh, The N K-edge X-ray absorption near edge structure (XANES) spectra of the purine-containing nucleotide, guanosine 5'-monophosphate (GMP), in aqueous solution are measured under various pH conditions. The spectra show characteristic peaks, which originate from resonant excitations of N 1s electrons to pi* orbitals inside the guanine moiety of GMP. The relative intensities of these peaks depend on the pH values of the solution. The pH dependence is explained by the core-level shift of N atoms at specific sites caused by protonation and deprotonation. The experimental spectra are compared with theoretical spectra calculated by using density functional theory for GMP and the other purine-containing nucleotides, adenosine 5'-monophosphate, and adenosine 5'-triphosphate. The N K-edge XANES spectra for all of these nucleotides are classified by the numbers of N atoms with particular chemical bonding characteristics in the purine moiety. (C) 2014 AIP Publishing LLC., AMER INST PHYSICS
    JOURNAL OF CHEMICAL PHYSICS, 2014年08月, [査読有り]
  • 〔主要な業績〕Induction of genetic instability by transfer of a UV-A-irradiated chromosome
    Ayumi Urushibara; Seiji Kodama; Akinari Yokoya, Exposure of cells to ultraviolet (UV)-A radiation induces oxidative damage in DNA, such as 8-oxo-7,8-dihydroguanine (8-oxoG), single-strand breaks, a-basic sites, and DNA-protein cross-links, via reactions with reactive oxygen species (ROS). In this study we examine whether the damage other than double-strand breaks (non-DSB damage), which is UV-A-induced oxidative damage, plays a role in the induction of chromosomal instability. We exposed human chromosome 21 to UV-A and transferred the chromosome into non-irradiated mouse recipient cells by microcell-mediated chromosome transfer. The chromosomal instability of both the transferred human chromosome and the recipient mouse chromosomes was examined by whole-chromosome painting and fluorescence in situ hybridization (WCP-FISH). The ploidy of the mouse recipient cells increased, and chromosomal aberrations occurred not only in the UV-A-irradiated human chromosome but also in the non-irradiated mouse chromosomes. The frequencies of these abnormalities increased with the radiation dose received by the transferred human chromosome. In contrast, in the control experiment, in which an non-irradiated human chromosome was transferred, the micro-cell hybrids remained diploid, and the frequency of chromosomal aberrations in both the transferred human chromosome and recipient mouse chromosomes remained low. Thus, the present study indicates that a chromosome harboring non-DSB damage induced by UV-A irradiation is unstable and transmits instability to chromosomes of non-irradiated recipient mouse cells. (C) 2014 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
    MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2014年05月, [査読有り]
  • 〔主要な業績〕Structural changes of nucleic acid base in aqueous solution as observed in X-ray absorption near edge structure (XANES)
    Hiroyuki Shimada; Taishi Fukao; Hirotake Minami; Masatoshi Ukai; Kentaro Fujii; Akinari Yokoya; Yoshihiro Fukuda; Yuji Saitoh, X-ray absorption near edge structure (XANES) spectra for adenine-containing nucleotides, adenosine 5'-monophosphate (AMP) and adenosine 5'-triphosphate (ATP) in aqueous solutions at the nitrogen K-edge region were measured. The two intense peaks in XANES spectra are assigned to transitions of 1s electrons to the pi* orbitals of different types of N atoms with particular bonding characteristics. The difference between their spectra is ascribed to protonation of a particular N atom. Similarity observed in XANES spectra of guanosine 5'-monophosphate (GMP) and ATP is also interpreted as similar bonding characters of the N atoms in the nucleobase moiety. (C) 2013 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
    CHEMICAL PHYSICS LETTERS, 2014年01月, [査読有り]
  • Bond cleavages of adenosine 5 '-triphosphate induced by monochromatic soft X-rays
    K. Fujii; A. Narita; A. Yokoya, To investigate which type of bond is likely to be cleaved by soft X-ray exposure to an adenosine 5'-triphosphate (ATP), we observed spectral changes in X-ray absorption near edge structure (XANES) around nitrogen and oxygen K-edge of an ATP film by soft X-ray irradiation. Experiments were performed at a synchrotron soft X-ray beamline at SPring-8, Japan. The XANES spectra around the nitrogen and oxygen K-edge slightly varied by exposure to 560 eV soft X-rays. These changes are originated from the cleavage of C-N bonds between a sugar and a nucleobase site and of C-O, P-O or O-H bond of sugar and phosphate site. From the comparison between the change in XANES intensity of sigma* peak at nitrogen and that at oxygen K-edges, it is inferred that the C-O, P-O or O-H bond of sugar and phosphate is much efficiently cleaved than the C-N of N-glycoside bond by the exposure of 560 eV soft X-ray to ATP film., IOP PUBLISHING LTD
    1ST CONFERENCE ON LIGHT AND PARTICLE BEAMS IN MATERIALS SCIENCE 2013 (LPBMS2013), 2014年, [査読有り]
  • DNA damage by soft X-ray exposure at oxygen K-edge
    Y. Sugaya; A. Narita; K. Fujii; A. Yokoya, 責任著者, In order to obtain detailed insights into the physicochemical mechanism of DNA damage induction in terms of photoabsorption modes, we have prepared thin DNA films of closed circular plasmid (pUC18) on a cover slip without any additives. Using this film, we have performed preliminary experiments by exposing to soft X-rays with energies around oxygen K-shell ionization threshold. The DNA damage yields of strand breaks and base lesions or AP sites were quantified by biochemical treatments. We confirmed that the DNA film can work as a specimen irradiation. The DNA damage yields induced by pi* excitation of a K-shell electron of oxygen atoms in DNA were significantly larger those for oxygen K-ionization., IOP PUBLISHING LTD
    1ST CONFERENCE ON LIGHT AND PARTICLE BEAMS IN MATERIALS SCIENCE 2013 (LPBMS2013), 2014年, [査読有り]
  • Significance of DNA polymerase I in in vivo processing of clustered DNA damage
    Naoya Shikazono; Ken Akamatsu; Momoko Takahashi; Miho Noguchi; Ayumi Urushibara; Peter O'Neill; Akinari Yokoya, We examined the biological consequences of bi-stranded clustered damage sites, consisting of a combination of DNA lesions, such as a 1-nucleotide gap (GAP), an apurinic/apyrimidinic (AP) site, and an 8-oxo-7,8-dihydroguanine (8-oxoG), using a bacterial plasmid-based assay. Following transformation with the plasmid containing bi-stranded clustered damage sites into the wild type strain of Escherichia coli, transformation frequencies were significantly lower for the bi-stranded clustered GAP/AP lesions (separated by 1 bp) than for either a single GAP or a single AP site. When the two lesions were separated by 10-20 bp, the transformation efficiencies were comparable with those of the single lesions. This recovery of transformation efficiency for separated lesions requires DNA polymerase I (Pol I) activity. Analogously, the mutation frequency was found to depend on the distance separating lesions in a bi-stranded cluster containing a GAP and an 8-oxoG, and Poll was found to play an important role in minimising mutations induced as a result of clustered lesions. The mutagenic potential of 8-oxoG within the bi-stranded lesions does not depend on whether it is situated on the leading or lagging strand. These results indicate that the biological consequences of clustered DNA damage strongly depend on the extent of repair of the strand breaks as well as the DNA polymerase in lesion-avoidance pathways during replication. (C) 2013 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
    MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2013年09月, [査読有り]
  • 〔主要な業績〕Chemical repair of base lesions, AP-sites, and strand breaks on plasmid DNA in dilute aqueous solution by ascorbic acid
    Kuniki Hata; Ayumi Urushibara; Shinichi Yamashita; Naoya Shikazono; Akinari Yokoya; Yosuke Katsumura, We quantified the damage yields produced in plasmid DNA by gamma-irradiation in the presence of low concentrations (10-100 mu M) of ascorbic acid, which is a major antioxidant in living systems, to clarify whether it chemically repairs radiation damage in DNA. The yield of DNA single strand breaks induced by irradiation was analyzed with agarose gel electrophoresis as conformational changes in closed circular plasmids. Base lesions and abasic sites were also observed as additional conformational changes by treating irradiated samples with glycosylase proteins.
    By comparing the suppression efficiencies to the induction of each DNA lesion, in addition to scavenging of the OH radicals derived from water radiolysis, it was found that ascorbic acid promotes the chemical repair of precursors of AP-sites and base lesions more effectively than those of single strand breaks. We estimated the efficiency of the chemical repair of each lesion using a kinetic model. Approximately 50-60% of base lesions and AP-sites were repaired by 10 mu M ascorbic acid, although strand breaks were largely unrepaired by ascorbic acid at low concentrations. The methods in this study will provide a route to understanding the Mechanistic aspects of antioxidant activity in living systems. (C) 2013 Elsevier Inc. All rights reserved., ACADEMIC PRESS INC ELSEVIER SCIENCE
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013年05月, [査読有り]
  • 〔主要な業績〕Induction of DNA damage, including abasic sites, in plasmid DNA by carbon ion and X-ray irradiation
    Takuya Shiina; Ritsuko Watanabe; Iyo Shiraishi; Masao Suzuki; Yuki Sugaya; Kentaro Fujii; Akinari Yokoya, 責任著者, DNA from plasmid pUC18 was irradiated with low-LET (13 keV/mu m) or high-LET (60 keV/mu m) carbon ions or X-rays (4 keV/mu m) in solutions containing several concentrations of Tris (0.66-200 mM) to determine the yield of abasic (AP) sites and the effect of scavenging capacity. The yield of AP sites, detected as single-strand breaks (SSB) after digestion with E. coli endonuclease IV (Nfo), was compared with that of SSB and base lesions. At higher concentrations of Tris, the yields of single or clustered AP sites were significantly lower than those of single or clustered base lesions. The relative yields of single AP sites and AP clusters were less than 10 and 7 %, respectively, of the total damage produced at a scavenger capacity mimicking that in cells. The dependence of the yield of AP sites on scavenging capacity was similar to that of prompt strand breaks. The ratios of the yield of isolated AP sites to that of SSB induced by carbon ion or X-ray irradiation were relatively constant at 0.45 +/- A 0.15 over the tested range of scavenger capacity, although the ratio of SSB to double-strand breaks (DSB) showed the characteristic dependence on both scavenging capacity and radiation quality. These results indicate that the reaction of water radiolysis products, presumably OH radicals, with the sugar-phosphate moieties in the DNA backbone induces both AP sites and SSB with similar efficiency. Direct ionization of DNA is notably more involved in the production of DSB and base lesion clusters than in the production of AP site clusters., SPRINGER
    RADIATION AND ENVIRONMENTAL BIOPHYSICS, 2013年03月, [査読有り]
  • Lifetime of the unpaired electron species in calf thymus DNA thin films induced by nitrogen and oxygen K-shell photoabsorption
    Toshitaka Oka; Akinari Yokoya; Kentaro Fujii, Purpose : To study the lifetime of the short-lived unpaired electron species induced in a calf thymus DNA film by soft X-rays in the energy regions around nitrogen and oxygen K-edge.
    Materials and methods : Dry calf thymus DNA films were measured by electron paramagnetic resonance (EPR) spectrometer during the monochromatic soft X-ray irradiation provided from a synchrotron accelerator (SPring-8, Super Photon ring-8 GeV). Two operation modes of SPring-8 with different electron bunch structures were used to explore dependence of EPR intensity on pulse interval of soft X-rays.
    Results : Observed EPR spectra did not show significant difference, in the spectral shape, intensity, g-factor and photon energy dependence, between the two bunch modes.
    Conclusions : The total yield of the unpaired electron species were estimated by assuming the exponential relaxation of the unpaired electrons with two different bunch modes of the synchrotron. The lifetime of the unpaired electron species is estimated to be in the range of a few tens to several hundreds of mu s., INFORMA HEALTHCARE
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2012年12月, [査読有り]
  • Observation of cleavage in DNA and nucleotides following oxygen K-shell ionization by measuring X-ray absorption near edge structure
    Kentaro Fujii; Yoshihiro Fukuda; Akinari Yokoya, Purpose: To investigate which type of bond is more likely to be cleaved in functional groups in DNA including the nucleobases by the K-shell ionization of oxygen of DNA, and to determine whether the production of propenal is specific to the oxygen resonant excitation. To investigate the degradation pattern which depends on the type of nucleobase in the DNA monomer.
    Materials and methods: Calf thymus DNA film and four nucleotides (dAMP, TMP, dGMP, and dCMP) films were used as samples. Soft X-rays with energy of 560 eV were used to irradiate the samples, and the changes in the X-ray absorption near edge structure (XANES) spectra during the irradiation were measured. The XANES measurements were performed by using a 0.02 eV scanning photon energy step.
    Results: The difference spectra for DNA and nucleotides were similar to those for pyridine deprotonation. The oxygen K-edge regions in the difference spectra were all similar apart from the spectrum obtained at the resonant excitation energy of oxygen in DNA. The spectral change did not depend on the type of nucleotide.
    Conclusion: (1) Deprotonation of the nucleobase -NH is usually induced by core ionization of carbon, nitrogen, and oxygen; (2) propenal production is specific to the oxygen K-shell resonant excitation; and (3) the pattern of XANES spectral changes does not significantly depend on the type of nucleobase., INFORMA HEALTHCARE
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2012年12月, [査読有り]
  • Development of a simulation method for dynamics of electrons ejected from DNA molecules irradiated with X-rays
    Takeshi Kai; Mariko Higuchi; Kentaro Fujii; Ritsuko Watanabe; Akinari Yokoya, Purpose: To develop a method for simulating the dynamics of the photoelectrons and Auger electrons ejected from DNA molecules irradiated with pulsed monochromatic X-rays.
    Materials and methods: A 30-base-pair (bp) DNA molecule was used as the target model, and the X-rays were assumed to have a Gaussian-shaped time distribution. Photoionization and Auger decay were considered as the atomic processes. The atoms from which the photoelectrons or Auger electrons were emitted were specified in the DNA molecule (or DNA ion) using the Monte Carlo method, and the trajectory of each electron in the electric field formed around the positively charged DNA molecule was calculated with a Newtonian equation. The kinetics of the electrons produced by irradiation with X-rays at an intensity ranging from 1 x 10(12) to 1 x 10(16) photons/mm(2) and energies of 380 eV (below the carbon K-edge), 435 eV (above the nitrogen K-edge), and 560 eV (above the oxygen K-edge) were evaluated.
    Results: It was found that at an X-ray intensity of 1 x 10(14) photons/mm(2) or less, all the produced electrons escaped from the target. However, above an X-ray intensity of 1 x 10(15) photons/mm(2) and an energy of 560 eV, some photoelectrons that were ejected from the oxygen atoms were trapped near the target DNA.
    Conclusions: A simulation method for studying the trajectories of electrons ejected from a 30-bp DNA molecule irradiated with pulsed monochromatic X-rays has been developed. The present results show that electron dynamics are strongly dependent on the charged density induced in DNA by pulsed X-ray irradiation., INFORMA HEALTHCARE
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2012年12月, [査読有り]
  • 〔主要な業績〕Unpaired Electron Species in Thin Films of Calf-Thymus DNA Molecules Induced by Nitrogen and Oxygen K-Shell Photoabsorption
    T. Oka; A. Yokoya; K. Fujii; Y. Fukuda; M. Ukai, The mechanism of DNA modification induced by K-shell photoabsorption of nitrogen and oxygen atoms was investigated by electron paramagnetic resonance and x-ray absorption near edge structure measurements of calf thymus DNA. A g factor of 2.000 for the unpaired electron species, which only arises during irradiation, was measured. The EPR intensities for DNA zwere twofold times larger than those estimated based on the photoabsorption cross section. This suggests that the DNA film itself forms unpaired electron species through the excitation of enhanced electron recapturing, known as the postcollision interaction process., AMER PHYSICAL SOC
    PHYSICAL REVIEW LETTERS, 2012年11月, [査読有り]
  • 〔主要な業績〕Yield of Single- and Double-Strand Breaks and Nucleobase Lesions in Fully Hydrated Plasmid DNA Films Irradiated with High-LET Charged Particles
    Takeshi Ushigome; Naoya Shikazono; Kentaro Fujii; Ritsuko Watanabe; Masao Suzuki; Chizuru Tsuruoka; Hiroshi Tauchi; Akinari Yokoya, 責任著者, We measured the yield and spectrum of strand breaks and nucleobase lesions produced in fully hydrated plasmid DNA films to determine the linear energy transfer (LET) dependence of DNA damage induced by ion-beam irradiation in relation to the change in the atomic number of ions. The yield of isolated damage was revealed as a decrease in prompt SSBs with increasing LET of He2+, C5+6+ and Ne-8+,Ne-10+ ions. On the other hand, the yields of prompt DSBs increased with increasing ion LET. SSBs were additionally induced in ion-irradiated DNA film by treatment with two kinds of base excision repair proteins (glycosylases), Nth and Fpg, indicating that base lesions are produced in the hydrated DNA film. This result shows that nucleobase lesions are produced via both chemical reactions with diffusible water radicals, such as OH radicals, and direct energy deposition onto DNA and the hydrated water layer. Nth-sensitive sites deduced to be pyrimidine lesions, such as 5,6-dihydrothymine (DHT), showed a relatively larger yield than Fpg-sensitive sites deduced to be purine lesions, such as 7,8-dihydro-8-oxo-2'deoxyguanine (8-oxoGua), for all ion exposures tested. The yield of SSBs or DSBs observed by enzyme treatment decreased noticeably with increasing LET for all tested ions. These results indicated that higher-LET ions preferentially produce a complex type of damage that might compromise the activities of the glycosylases used in this study. These findings are biologically important since, under cell mimicking conditions, persistent DNA damage occurs in part due to direct energy deposition on the DNA or hydrated water shell that is specifically induced by dense ionization in the track. (C) 2012 by Radiation Research Society, RADIATION RESEARCH SOC
    RADIATION RESEARCH, 2012年05月, [査読有り]
  • 〔主要な業績〕The mutagenic potential of 8-oxoG/single strand break-containing clusters depends on their relative positions
    Miho Noguchi; Ayumi Urushibara; Akinari Yokoya; Peter O'Neill; Naoya Shikazono, The biological consequences of clusters containing a single strand break and base lesion(s) remain largely unknown. In the present study we determined the mutagenicities of two- and three-lesion clustered damage sites containing a 1-nucleotide gap (GAP) and 8-oxo-7,8-dihydroguanine(s) (8-oxoG(s)) in Escherichia coli. The mutation frequencies (MFs) of bi-stranded two-lesion clusters (GAP/8-oxoG), especially in mutY-deficient strains, were high and were similar to those for bi-stranded clusters with 8-oxoG and base lesions/AP sites, suggesting that the GAP is processed with an efficiency similar to the efficiency of processing a base lesion or an AP site within a cluster. The MFs of tandem two-lesion clusters comprised of a GAP and an 8-oxoG on the same strand were comparable to or less than the MF of a single 8-oxoG. The mutagenic potential of three-lesion clusters, which were comprised of a tandem lesion (a GAP and an 8-oxoG) and an opposing single 8-oxoG, was higher than that of a single 8-oxoG, but was no more than that of a bi-stranded 8-oxoGs. We suggest that incorporation of a nucleotide opposite 8-oxoG is less mutagenic when a GAP is present in a cluster than when a GAP is absent. Our observations indicate that the repair of a GAP is retarded by an opposing 8-oxoG, but not by a tandem 8-oxoG, and that the extent of GAP repair determines the biological consequences. (C) 2012 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
    MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2012年04月, [査読有り]
  • 〔主要な業績〕Electron paramagnetic resonance study of unpaired electron species in thin films of pyrimidine bases induced by nitrogen and oxygen K-shell photoabsorption
    T. Oka; A. Yokoya; K. Fujii, In order to clarify the mechanism of DNA-base modification induced by K-shell photoabsorption of nitrogen and oxygen atoms, we measured electron paramagnetic resonance (EPR) spectra of two DNA pyrimidine bases, thymine, and cytosine. The g-factor of 2.000 of the unpaired electron species arising only during irradiation is determined. The EPR intensities for cytosine are two times larger than those simply estimated based on the photoabsorption cross section, whereas those for thymine show similar energy dependence to photoabsorption spectra, suggesting that cytosine favors to form unpaired electron species, rather than thymine, presumably due to the excitation of the enhanced electron capturing. (C) 2011 American Institute of Physics. [doi:10.1063/1.3563712], AMER INST PHYSICS
    APPLIED PHYSICS LETTERS, 2011年03月, [査読有り]
  • A MODEL FOR ANALYSIS OF THE YIELD AND THE LEVEL OF CLUSTERING OF RADIATION-INDUCED DNA-STRAND BREAKS IN HYDRATED PLASMIDS
    N. Shikazono; A. Yokoya; A. Urushibara; M. Noguchi; K. Fujii, Although it is widely accepted that the spatial distribution of strand breaks is highly relevant to the biological consequences of radiation, the extent to which strand breaks are clustered is not usually demonstrated directly from the experimental data. To evaluate the spatial distribution of radiation-induced strand breaks, the authors have developed a model for the generation of strand breaks after irradiation. The model assumes that (1) a radiation track has a certain probability of ` hitting' a plasmid, (2) the radiation generates strand break(s) by chance within a relatively small region that could produce doublestrand breaks and (3) the number of strand breaks generated within the region follows a Poisson distribution. To find out whether the model is valid, the authors compared the calculated values with the experimental data obtained by a plasmid DNA assay. Taking into account the inherent bias of the plasmid assay, the model described well the experimental results of hydrated plasmids exposed to radiation., OXFORD UNIV PRESS
    RADIATION PROTECTION DOSIMETRY, 2011年02月, [査読有り]
  • A NOVEL TECHNIQUE USING DNA DENATURATION TO DETECT MULTIPLY INDUCED SINGLE-STRAND BREAKS IN A HYDRATED PLASMID DNA MOLECULE BY X-RAY AND He-4(2+) ION IRRADIATION
    Akinari Yokoya; Naoya Shikazono; Kentaro Fujii; Miho Noguchi; Ayumi Urushibara, 筆頭著者, To detect multiple single-strand breaks (SSBs) produced in plasmid DNA molecules by direct energy deposition from radiation tracks, we have developed a novel technique using DNA denaturation by which irradiated DNA is analysed as single-strand DNA (SS-DNA). The multiple SSBs that arise in both strands of DNA, but do not induce a double-strand break, are quantified as loss of SS-DNA using agarose gel electrophoresis. We have applied this method to X-ray and He-4(2+) ion-irradiated samples of fully hydrated pUC18 plasmid DNA. The fractions of both SS-DNA and closed circular DNA (CCDNA) exponentially decrease with the increasing dose of X rays and He-4(2+) ions. The efficiency of the loss of SS-DNA was half that of CC-DNA for both types of irradiation, indicating that one of two strands in DNA is not broken when one SSB is produced in CC-DNA by irradiation. Contrary to our initial expectation, these results indicate that SSBs are not multiply induced even by high linear energy transfer radiation distributed in both strands., OXFORD UNIV PRESS
    RADIATION PROTECTION DOSIMETRY, 2011年02月, [査読有り]
  • Protective effects of silybin and analogues against X-ray radiation-induced damage
    Haiying Fu; Mingzhang Lin; Yosuke Katsumura; Akinari Yokoya; Kuniki Hata; Yusa Muroya; Kentaro Fujii; Naoya Shikazono, Silybin (SLB) and similar analogues, namely, hesperetin (HESP), naringenin (NAN) and naringin (NAR), are believed to be active constituents of natural flavonoids that have been reported as chemopreventive agents for certain cancers. Moreover, SLB and analogues have been determined to fast repair DNA bases from oxidative damage by pulse radiolysis techniques. The present study was designed to evaluate the protective effects of SLB and analogues on soft X-ray-induced damage to plasmid DNA in vitro. The DNA damage was determined by agarose gel electrophoresis. SLB and analogues were found to protect DNA from radiation damage at micromolar concentrations. Among the compounds tested, HESP and SLB were the most effective in preventing X-ray-induced formation of DNA single-strand breaks (SSB). A comparison of these results with other experiments showed that the ability of SLB and analogues to inhibit DNA damage in vitro correlated with the ability of the compounds to scavenge free radicals. Our work revealed that natural flavonoids, SLB and analogues may be used as potent radioprotectors against radiation damage., OXFORD UNIV PRESS
    ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2010年07月, [査読有り]
  • 〔主要な業績〕X-ray absorption spectra of nucleotides (AMP, GMP, and CMP) in liquid water solutions near the nitrogen K-edge
    Masatoshi Ukai; Akinari Yokoya; Kentaro Fujii; Yuji Saitoh, The X-ray absorption of nucleotides (adenosine-5'-monophosphate, guanosine 5'-monophosphate, and cytidine 5'-monophosphate) are measured in both water solutions and thin solid films at X-ray energies near the nitrogen K-edge in the 'water-window' region. Each spectrum corresponds to the selective excitation of a nucleobase site in a nucleotide, and thus has features similar to the spectrum of the corresponding nucleobase. An additional new peak in the energy region of the nitrogen 1s -> pi* resonance is observed for each nucleotide. No significant difference between the water solutions and thin solid films is found, which might be attributable to the hydrophobic properties of a nucleobase in a nucleotide. (C) 2010 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
    CHEMICAL PHYSICS LETTERS, 2010年07月, [査読有り]
  • Spectral change in X-ray absorption near edge structure of DNA thin films irradiated with monochromatic soft X-rays
    Kentaro Fujii; Akinari Yokoya, To reveal the chemical changes induced in DNA by irradiation with ionizing radiation, we have investigated the spectral change in the X-ray absorption near edge structure (XANES) of DNA resulting from exposure to monochromatic soft X-rays. We used a thin film of calf thymus DNA as a sample and observed nitrogen K-shell and oxygen K-shell XANES spectra. The typical monochromatic soft X-ray energies used for the irradiation (395, 408, 528, and 538 eV) were obtained from a soft X-ray beamline (BL23SU, SPring-8). These energies correspond to those just below or just above the nitrogen and oxygen K-shell ionization energy, respectively. The obtained XANES spectra show significant changes by irradiation. Particularly a new pi* resonance peak in oxygen XANES spectra evidently appeared by the irradiation above oxygen K-shell ionization potential. These results suggest that carbonyl groups, presumably a propenal group (O=C-C=C), may be produced in the sample by oxygen ionization. Thus characteristic damage induced by induction in the DNA molecule would be predicted following exposure to monochromatized synchrotron soft X-rays. (C) 2009 Elsevier Ltd. All rights reserved., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2009年12月, [査読有り]
  • Free radical scavenging and radioprotective effects of carnosine and anserine
    Haiying Fu; Yosuke Katsumura; Mingzhang Lin; Yusa Muroya; Kuniki Hata; Kentaro Fujii; Akinari Yokoya; Yoshihiko Hatano, Two histidine-containing natural dipeptides, carnosine and anserine (beta-alanyl-1-methyl-L-histidine), have been examined for their antioxidant and radioprotective abilities. Pulse radiolysis studies indicated the antioxidative properties of carnosine and anserine aqueous solutions at different pH. The rate constants for the reaction CH radical with carnosine at neutral pH were determined to be 5.3 x 10(9) M-1 s(-1) at 300 nm, and 4.1 x 10(9) M-1 s(-1) at 400 nm, respectively. Carnosine and anserine also protected plasmid pUC18 DNA from X-ray radiation-induced strand breaks as evidenced from the studies by agarose gel electrophoresis, Carnosine showed higher protective efficiency under the experimental conditions. Our data demonstrated that carnosine and anserine may play an important role in the maintenance of the antioxidant system. (C) 2009 Elsevier Ltd. All rights reserved., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2009年12月, [査読有り]
  • Synchrotron radiation photoelectron studies for primary radiation effects using a liquid water jet in vacuum: Total and partial photoelectron yields for liquid water near the oxygen K-edge
    Masatoshi Ukai; Akinari Yokoya; Yusuke Nonaka; Kentaro Fujii; Yuji Saitoh, A new spectroscopy to identify the hydration structure playing important role in liquid-phase radiation damage is in progress using a laminar liquid water jet sample in vacuum in combination with soft X-ray synchrotron radiation. We present the total and partial electron yields for liquid water using a photoelectron spectroscopy. Partial electron yields for the K-1 1b(1) 1b(1), Auger transition are obtained for the first time by measuring the electrostatically dispersed electron kinetic energy spectra as a function of photon energy of synchrotron radiation. (C) 2009 Published by Elsevier Ltd., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2009年12月, [査読有り]
  • EPR study of radiation damage to DNA irradiated with synchrotron soft X-rays around nitrogen and oxygen K-edge
    A. Yokoya; K. Fujii; Y. Fukuda; M. Ukai, 筆頭著者, In order to obtain detailed insights into the physicochemical mechanism of DNA damage induction, "in situ" measurement of electron paramagnetic resonance (EPR) signal from DNA constituent nucleobases, guanine and adenine, has been performed in a vacuum using monochromatic synchrotron soft X-rays. We found that short-lived unpaired electron species arise only during irradiation to the evaporated thin film on a surface. The EPR spectrum of the short-lived species significantly depends on the photon energy irradiated, and the spin concentration obtained from the EPR spectra shows a similar fine structure to the X-ray photoabsorption spectra (X-ray absorption near edge structure: XANES). For the adenine sample, the spin concentration alters strikingly by water absorption on the sample surface. Trapping of photo- or Auger electrons into a newly generated potential in the nucleobases as the consequence of photoelectric effect is suggested as mechanisms of the induction of the short-lived species. (C) 2009 Elsevier Ltd. All rights reserved., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2009年12月, [査読有り]
  • Nucleobase Lesions and Strand Breaks in Dry DNA Thin Film Selectively Induced by Monochromatic Soft X-rays
    Kentaro Fujii; Naoya Shikazono; Akinari Yokoya, To verify the possibility of "selective damage induction" in DNA, the yields of base lesions as well as strand breaks have been measured in dry plasmid DNA films irradiated with highly monochromatized soft X-rays in the energy region of 270-760 eV, which includes the carbon, nitrogen, and oxygen K-edges. The yields of both pyrimidine and purine base lesions, observed as Nth-sensitive and Fpg-sensitive sites, respectively, are strikingly high at the oxygen K-edge (560 eV) but extremely low at an energy just below the nitrogen K-edge (380 eV) as compared with the yields observed at other photon energies. The yields at 560 eV are enhanced 9.6-fold and 27-fold for Nth-sensitive and Fpg-sensitive sites, respectively, compared with those at 380 eV. The yield of prompt single strand breaks is also enhanced at the oxygen K-ionization energy, but only 2-fold, as compared with that at 380 eV. Our results strongly suggest that (1) the K-shell ionization of oxygen in both the nucleobases as well as in other parts of DNA and in the hydrating water molecules bound to DNA, but not the K-shell ionization of nitrogen in the nucleobases, most likely contributes to the induction of nucleobase lesions and that (2) migration of electrons and holes is involved differentially in the production of each type of DNA lesion. These results could potentially lead to new methods for "partially selective induction" of specific types of DNA damage through tuning the energy of soft X-rays., AMER CHEMICAL SOC
    JOURNAL OF PHYSICAL CHEMISTRY B, 2009年12月, [査読有り]
  • 〔主要な業績〕Induction of DNA Strand Breaks, Base Lesions and Clustered Damage Sites in Hydrated Plasmid DNA Films by Ultrasoft X Rays around the Phosphorus K Edge
    Akinari Yokoya; Siobhan M. T. Cunniffe; Ritsuko Watanabe; Katsumi Kobayashi; Peter O' Neill, 筆頭著者, To characterize the DNA damage induced by K-shell ionization of phosphorus atom in DNA backbone on the level of hydration, the yields of DNA strand breaks and base lesions arising from the interaction of ultrasoft X rays with energies around the phosphorus K edge were determined using dry and fully hydrated pUC18 plasmid DNA samples. Base lesions and bistranded clustered DNA damage sites were revealed by postirradiation treatment with the base excision repair proteins endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg). The yield of prompt single-strand breaks (SSBs) with dry DNA irradiated at the phosphorus K resonance energy (2153 eV) is about one-third that below the phosphorus K edge (2147 eV). The yields of prompt double-strand breaks (DSBs) were found to be less dependent on the X-ray energy, with the yields being about two times lower when irradiated at 2153 eV. Heat-labile sites were not produced in detectable amounts. The yields of base lesions were dependent on the energy of the X rays, especially when the DNA was fully hydrated. Bistranded clustered DNA damage sites, revealed enzymatically as additional DSBs, were produced in dry as well as in hydrated DNA with all three energies of X rays. The yields of these enzyme-sensitive sites were also lower when irradiated at the phosphorus K resonance energy. On the other hand, the yields of prompt SSBs and enzyme-sensitive sites for the two off-resonance energies were, larger than those determined previously for gamma radiation. The results indicate that the photoelectric effect caused by X rays and dense ionization and excitation events along the tracks of low-energy secondary electrons are more effective at inducing SSBs and enzyme-sensitive sites. The complex types of damage, prompt and enzymatically induced DSBs, are preferentially induced by phosphorus K resonance at 2153 eV rather than simple SSBs and isolated base lesions, particularly in hydrated conditions. It is concluded that not only the phosphorus K resonance and resulting emission of low-energy LMM-Auger electrons (similar to 120 eV) but also the level of hydration plays an important role in the induction of complex damage in plasmid DNA. (C) 2009 by Radiation Research Society, RADIATION RESEARCH SOC
    RADIATION RESEARCH, 2009年09月, [査読有り]
  • The Yield, Processing, and Biological Consequences of Clustered DNA Damage Induced by Ionizing Radiation
    Naoya Shikazono; Miho Noguchi; Kentaro Fujii; Ayumi Urushibara; Akinari Yokoya, After living cells are exposed to ionizing radiation, a variety of chemical modifications of DNA are induced either directly by ionization of DNA or indirectly through interactions with water-derived radicals. The DNA lesions include single strand breaks (SSB), base lesions, sugar damage, and apurinic/apyrimidinic sites (AP sites). Clustered DNA damage, which is defined as two or more of such lesions within one to two helical turns of DNA induced by a single radiation track, is considered to be a unique feature of ionizing radiation. A double strand break (DSB) is a type Of Clustered DNA damage, in which single strand breaks arc formed on opposite strands in close proximity. Fort-nation and repair of DSBs have been studied in great detail over the years as they have been linked to important biological endpoints, such as cell death, loss of genetic material, chromosome aberration. Although non-DSB clustered DNA damage has received less attention, there is growing evidence of its biological significance. This review focuses on the current understanding of (1) the yield of non-DSB clustered damage induced by ionizing radiation (2) the processing, and (3) biological consequences of non-DSB clustered DNA damage., JAPAN RADIATION RESEARCH SOC
    JOURNAL OF RADIATION RESEARCH, 2009年01月, [査読有り]
  • Free radical scavenging reactions and antioxidant activities of silybin: Mechanistic aspects and pulse radiolytic studies
    Haiying Fu; Mingzhang Lin; Yusa Muroya; Kuniki Hata; Yosuke Katsumura; Akinari Yokoya; Naoya Shikazono; Yoshihiko Hatano, Silybin (extracted from Silybum marianum) is the major active constituent of silymarin which possesses a wide range of medicinal properties. These properties may be, in part, due to the potent scavenging capacity of oxidizing free radicals. In this context, scavenging radicals (hydroxyl, azide, dibromide anion radicals, nitrite, carbonate, etc.) of silybin have been studied to understand the mechanistic aspects of its action against free radicals. The transients produced in these reactions have been assigned and the rate constants have been measured by pulse radiolysis techniques. Reduction potential determined both by cyclic voltammetry gave a value 0.62 +/- 0.02 V vs NHE at pH 9. Quantum chemical calculations have been performed to further confirm the different activities of individual hydroxyl groups with the difference of heat of formation. Moreover, silybin also protected plasmid pUC18 DNA from soft X-ray radiation which induced strand breaks. These results are expected to be helpful for a better understanding of the anti-oxidative properties of silybin., TAYLOR & FRANCIS LTD
    FREE RADICAL RESEARCH, 2009年, [査読有り]
  • Studies of soft X-ray-induced Auger effect on the induction of DNA damage
    A. Yokoya; K. Fuji; N. Shikazono; K. Akamatsu; A. Urushibara; R. Watanabe, Purpose: To understand the characteristics of DNA damage induced by Auger effect in DNA by ultrasoft X-irradiation. In situ electron paramagnetic resonance (EPR) spectroscopy as well as biochemical analysis has been applied to examine the DNA damage induction in both viewpoints of intermediate species and final products.
    Materials and methods: Unpaired electron species induced in a calf thymus DNA film irradiated with monochromatic ultrasoft X-rays (270-580 eV) was observed using an X-band EPR spectrometer installed in a synchrotron beamline. To determine the yield of single strand break (SSB), pUC18 plasmid DNA was irradiated and then analyzed by agarose gel electrophoresis. To analyze molecular change in a single strand DNA, a new technique using DNA-denaturation-treatment has been applied to quantify multiple SSB arising in both DNA strands.
    Results: Short-lived EPR spectra were observed during irradiation. The intensity of transient EPR spectrum shows the similar energy dependence with that of the SSB yield around oxygen K-edge in particular. The fraction of the single-strand plasmid DNA (SS-DNA) after irradiation could be determined using a low-temperature-denaturation condition. The obtained slope of the dose-response for SS-DNA shows half of that of closed circular DNA as expected under the diluted solution condition.
    Conclusion: The availability of an EPR apparatus installed in a synchrotron beamline is demonstrated by detecting very short-lived unpaired electron species. Transient EPR spectra of DNA show the similar energy dependence to that of the SSB yield. The proposed DNA-denaturation assay works as expected using the low-temperature-denaturation condition., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2008年12月, [査読有り]
  • Characterization of lesions induced in linear-formed plasmid DNA by valence ionization and Auger decay at carbon, nitrogen and oxygen
    Ken Akamatsu; Kentaro Fujii; Akinari Yokoya, Purpose: To study the DNA lesions induced by the Auger decay of carbon, nitrogen, and oxygen using ultrasoft X-rays (USX) that are expected to be important with the DNA repair system of living cells.
    Materials and methods: pUC19 plasmid DNA dry samples were irradiated with USX photons at 270 and 560 eV and (60)Co gamma-rays in vacuum at room temperature. The amounts of unaltered base release by the direct radiation effects were quantified using high-performance liquid chromatography. To quantify and characterize the strand break termini the rate at which snake venom phosphodiesterase (SVPD) digested irradiated DNA pretreated with and without calf intestine alkaline phosphatase was measured. Moreover, the pipcridine-labile base lesions and abasic sites of the irradiated DNA were estimated using the SVPD method.
    Results: The yields of unaltered base release for 270, 560 eV photons and (60)Co gamma-rays were 0.0 16, 0.014, and 0.0 18 mu mol/J, respectively. The total 3' termini for the three kinds of photons were around 0.1 mu mol/J. The production of 3' termini with phosphate was found to be predominant with respect to that of 3'OH termini for the three kinds of radiation. The yield of piperidine-labile sites for 270 eV (similar to 0.1 mu mol/J) was slightly larger than that for 560 eV (similar to 0.07 mu mol/J) and also for gamma-rays (similar to 0. 082 mu mol/J).
    Conclusion: Although the Auger process in DNA-constituent atoms was expected to induce Auger-specific lesions in the molecule the chemical endpoints would have been covered with a large number of lesions produced from secondary electrons in the surrounding bulk DNA molecules. The present results, however, suggest that a low-energy electron field produced by the USX photons in the bulk DNA is basically not at all specific to DNA damage being produced when compared with the high-energy electron field produced by (60)Co gamma-rays., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2008年12月, [査読有り]
  • Induction of single strand breaks, and base lesions in plasmid DNA films induced by carbon, nitrogen, and oxygen KLL Auger process
    Kentaro Fujii; Akinari Yokoya; Naoya Shikazono, Purpose: To reveal the reaction process in DNA by Auger electrons using the observed single strand breaks (SSB) and base lesions induced by monochromatic ultrasoft X-rays in dry plasmid DNA film. Desorbed ions from DNA and 2-deoxy-Dribose thin films were also measured to ascertain the decomposition site in DNA.
    Materials and methods: Dry plasmid DNA (pUC18) films were irradiated with synchrotron monochromatic ultrasoft X-rays (USX). Two photon energies, 270, and 560 eV, were chosen for the irradiation experiments. Irradiated plasmid DNA was analyzed by agarose gel electrophoresis. The yield of base lesions was determined by the post-irradiation-treatment of the DNA with enzymatic probes (formamidpyrimidine DNA glycosylase [Fpg] and endonuclease III [Nth]). Desorbed ions induced by 540 eV USX irradiation from calf thymus DNA and 2-deoxy-D-ribose thin films were detected by quadrupolemass spectrometer.
    Results: Yield of strand breaks and base lesions were obtained by 270 and 560 eV photon energies, respectively. Each yield showed characteristic of the photon energy spectrum. The characteristics of the desorbed ion mass spectra from 2-deoxy-Dribose and DNA films were strikingly similar with each other.
    Conclusions: In this paper we report, for the first time, the yields of base lesions and SSB induced by monochromatic USX. The yield of SSB induced by core-ionization of carbon, nitrogen, and oxygen was two times more frequent than that of valence-electrons. From the comparison of desorbed ion mass spectra of 2-deoxy-D-ribose with DNA films we predict these breaks are likely to be induced by the decomposition of the sugar sites in DNA backbone., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2008年12月, [査読有り]
  • ASR2007 - International symposium on "Charged Particle and Photon Interactions with Matter", November 6-9, 2007
    Y. Katsumura; M. Lin; A. Yokoya; Y. Hatano, PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2008年10月, [査読有り], [招待有り]
  • X-ray absorption spectrum for guanosine-5 '-monophosphate in water solution in the vicinity of the nitrogen K-edge observed in free liquid jet in vacuum
    Masatoshi Ukai; Akinari Yokoya; Kentaro Fujii; Yuji Saitoh, A new spectroscopy for direct effect of radiation damage to nucleic acids such as DNA and RNA is underway using a liquid beam sample in vacuum combined with soft-X-ray synchrotron radiation. We show the X-ray absorption spectrum (XANES) of liquid phase water at X-ray photon energy in the vicinity of oxygen K-shell absorption edge obtained from total photoelectron yields ejected from a pure water beam. We confirm a "liquid sample in vacuum" for the present experiment by the measurements of the temperature dependence of the XANES spectrum for a liquid beam of pure water. Shown is the first measurement of the XANES spectrum for guanosine-5'-monophosphate (GMP), which is one of the fundamental nucleotide unit for RNA, in water solution at X-ray photon energy in the vicinity of nitrogen K-shell absorption edge involved in the 'water-window' region, which corresponds to a selective excitation of guanine site. (C) 2008 Elsevier Ltd. All rights reserved., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2008年10月, [査読有り]
  • DNA damage induced by the direct effect of radiation
    A. Yokoya; N. Shikazono; K. Fujii; A. Urushibara; K. Akamatsu; R. Watanabe, 筆頭著者, We have studied the nature of DNA damage induced by the direct effect of radiation. The yields of single- (SSB) and double-strand breaks (DSB), base lesions and clustered damage were measured using the agarose gel electrophoresis method after exposing to various kinds of radiations to a simple model DNA molecule, fully hydrated closed-circular plasmid DNA (pUC18). The yield of SSB does not show significant dependence on linear energy transfer (LET) values. On the other hand, the yields of base lesions revealed by enzymatic probes, endonuclease III (Nth) and formamidopyrimidine DNA glycosylase (Fpg), which excise base lesions and leave a nick at the damage site, strongly depend on LET values. Soft X-ray photon (150 kVp) irradiation gives a maximum yield of the base lesions detected by the enzymatic probes as SSB and clustered damage, which is composed of one base lesion and proximate other base lesions or SSBs. The clustered damage is visualized as an enzymatically induced DSB. The yields of the enzymatically additional damages strikingly decrease with increasing levels of LET. These results suggest that in higher LET regions, the repair enzymes used as probes are compromised because of the dense damage clustering. The studies using simple plasmid DNA as a irradiation sample, however, have a technical difficulty to detect multiple SSBs in a plasmid DNA. To detect the additional SSBs induced in opposite strand of the first SSB, we have also developed a novel technique of DNA-denaturation assay. This allows us to detect multiply induced SSBs in both strand of DNA, but not induced DSB. (C) 2008 Elsevier Ltd. All rights reserved., PERGAMON-ELSEVIER SCIENCE LTD
    RADIATION PHYSICS AND CHEMISTRY, 2008年10月, [査読有り]
  • 〔主要な業績〕LET dependence of the yield of single-, double-strand breaks and base lesions in fully hydrated plasmid DNA films by He-4(2+) ion irradiation
    Ayumi Urushibara; Naoya Shikazono; Peter O'Neill; Kentaro Fujii; Seiichi Wada; Akinari Yokoya, Purpose: To characterize the complexity of DNA damage through determination of the yields of single (SSB) and double strand breaks (DSB), base lesions and clustered damage sites induced in fully hydrated plasmid DNA by direct radiation effects as a function of the ionizing density of the radiation using He-4(2+) ion irradiation with linear energy-transfer (LET) values in the range 19 to 148 keV/mu m.
    Materials and methods: Hydrated plasmid DNA (pUC 18) containing 34.5 water molecules/nucleotide was irradiated with He2+ ions with LET values of 19, 63, 95, 121 and 148 keV/mu m. From quantification of the conformational changes of the irradiated samples (closed circular, open or linear forms) analyzed by agarose gel electrophoresis, the yields of SSB and DSB were obtained. Base lesions were visualized as additional strand breaks by treatment with base excision repair enzymes (enclonuclease III (Nth) and formamidpyrimidine DNA glycosylase (Fpg)).
    Results: The yield of prompt SSB does not depend significantly on LET of the He-4(2+) ions, whereas the yield of prompt DSB increases with increasing LET. The yields of isolated base lesions, revealed by Nth and Fpg as additional SSB, decrease drastically with increasing LET. The sum of the yields of DSB and additional DSB revealed by Nth and Fpg increase with increasing LET of the He-4(2+) ions except at the highest LET investigated.
    Conclusion: The yields of clustered damage, revealed as DSB and non-DSB clustered damage sites, but not isolated lesions, namely SSB, increase with increasing ionization density of the He-4(2+) ions except at the highest LET investigated., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2008年01月, [査読有り]
  • DNA damage induced by the direct effect of HE ion particles
    Ayumi Urushibara; Naoya Shikazono; Ritsuko Watanabe; Kentaro Fujii; Peter O'Neill; Akinari Yokoya, We present here evidence showing that the yields of DNA lesions induced by He 21 ions strongly depend on Linear energy transfer (LET). In this study, hydrated plasmid DNA was irradiated with He2+ ions with LET values of 19, 63 and 95 keV mu m(-1). The yields of prompt single-strand breaks (SSBs) are very similar at the varying LET values, whereas the yields of prompt double-strand breaks (DSBs) increase with increasing LET. Further, base lesions were revealed as additional strand breaks by post-irradiation treatment of the DNA with endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg). The reduction in the yield of these enzymatically induced SSBs and DSBs becomes significant as the LET increases. These results suggest that the clustering of DNA lesions becomes more probable in regions of high LET., OXFORD UNIV PRESS
    RADIATION PROTECTION DOSIMETRY, 2006年12月, [査読有り]
  • Yields of strand breaks and base lesions induced by soft X-rays in plasmid DNA
    A. Yokoya; K. Fujii; T. Ushigome; N. Shikazono; A. Urushibara; R. Watanabe, 筆頭著者, The yields of soft-X-ray-induced DNA damages have been measured by using closed-circular plasmid DNA. Several DNA solutions with three kinds of radical scavenger capacity and also fully hydrated DNA samples were irradiated to compare the contribution by indirect reaction of diffusible water radicals, such as OH center dot, with those by direct action of secondary electrons. The yields of prompt single- (SSBs) and double-strand breaks (DSBs) decrease with increasing scavenging capacity. The SSB yields for soft X-rays are approximately midway those between gamma-ray and ultrasoft X-ray data previously reported. Heat labile sites are observed only in the low scavenger condition. The yields of the base lesions revealed by post irradiation treatment with base excision repair enzymes showed a similar value for Nth and Fpg protein except in the hydrated sample. These results indicate that the direct effect of soft X-rays induces the damages with different efficiency from those by indirect effect., OXFORD UNIV PRESS
    RADIATION PROTECTION DOSIMETRY, 2006年12月, [査読有り]
  • Natural circular dichroism of amino acid films observed in soft X-ray and VUV region using polarizing undulator
    K Nakagawa; F Kaneko; Y Ohta; M Tanaka; T Kitada; A Agui; F Fujii; A Yokoya; K Yagi-Watanabe; T Yamada, We observed the natural circular dichroism NCD of amino acid films in the soft X-ray region for the first time [M. Tanaka, K. Nakagawa, A. Agui, K. Fujii, A. Yokoya, Physica Scripta, in press]. Based on the success, a new generation of detection system is now under preparation. Vacuum ultraviolet NCD of amino acid films was measured successfully using a polarizing undulator [H. Onuki, Nucl. Instrum. Meth. A 246 (1986) 94] installed at the TERAS electron storage ring at AIST, Tsukuba, Japan. A result of NCD measurement for alanine films is described in detail. (c) 2005 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
    JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA, 2005年06月, [査読有り]
  • Chemical evolution of amino acid induced by soft X-ray with synchrotron radiation
    F Kaneko; M Tanaka; S Narita; T Kitada; T Matsui; K Nakagawa; A Agui; K Fujii; A Yokoya, Soft X-ray induced chemical evolution from glycine (Gly) to glycyl-glycine (glycine dimer or Gly-Gly) was studied for sublimated films of Gly. Values of quantum yield of Gly dimer formation were determined by high performance liquid chromatography (HPLC) technique to be: (1.2 +/- 0.2) x 10(-1) for 400 eV, (4.6 +/- 0.5) x 10(-2) for 407 eV and (3.2 +/- 1.5) x 10(-2) for 860 eV irradiation, respectively. We measured X-ray absorption spectra of irradiated Gly films at near edge region of nitrogen K-edge, as a function of X-ray dose. Formation of Gly-Gly was confirmed by the appearance and growth of 402 eV peak, which is a fingerprint of the peptide bond. The important role of surface to chemical evolution is discussed. (c) 2005 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
    JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA, 2005年06月, [査読有り]
  • 〔主要な業績〕First observation of natural circular dichroism for biomolecules in soft x-ray region studied with a polarizing undulator
    Masahito Tanaka; Kazumichi Nakagawa; Akane Agui; Kentaro Fujii; Akinari Yokoya, We measured natural circular dichroism (CD) for biomolecules in soft X-ray region for the first time. Natural linear dichroism (LD) for K(TiO)PO4 (KTP) crystal was also measured at the K-edge energy of oxygen. Measurements of CD and LD spectra were performed at the soft X-ray undulator beamline BL23SU of S Pring-8 in Japan. In this beamline, an APPLE-2 type variable undulator was installed as a light source. This undulator was operated under the phase modulation mode in which left and right circularly polarized light (LCPL and RCPL) was switched with about 0.1 Hz.
    As a sample for CD measurement, we used sublimated film of L-, D- and DL-phenylalanine (Phe) and L- and D-serine (Ser) (thickness similar to 300 nm) and measured CD (A(L)-A(R)) spectra in the nitrogen and the oxygen K-edge region, respectively. Here, A(L) and A(R) mean the abbreviation of absorption for LCPL and RCPL, respectively. For the Phe film, we observed a negative peak at about 407 eV for the L-Phe spectra. On the contrary, a positive peak for the D- Phe spectra and no spectral feature for the DL-Phe were observed. For the Ser film, we observed positive CD peaks at around 540 eV and 548eV at the L-Ser spectra, on the contrary, negative peaks for the D- Ser. These results are the first CD spectra for biomolecules in the soft X-ray region.
    We also used KTP crystal cut parallel to the plane (1,2,0) or (1,-2,0) as a sample of LD measurement and measured (A(L)-A(R)) spectra in the oxygen Kedge region and observed some peaks at about 530 eV. Since sign of these peaks were dependent on sample rotation angle in a plane perpendicular to the incident light, we concluded that these peaks are derived from linear anisotropy of crystal. Because of a weak linear polarization component of incident light, we could measure such LD spectra., IOP PUBLISHING LTD
    PHYSICA SCRIPTA, 2005年, [査読有り]
  • 〔主要な業績〕DNA strand breaks by direct energy deposition by Auger and photo-electrons ejected from DNA constituent atoms following K-shell photoabsorption
    R Watanabe; A Yokoya; K Fujii; K Saito, Purpose: To study DNA strand breaks induced by direct energy deposition by photo- and Auger electrons ejected following K-shell photoabsorption of DNA constituent atoms (carbon, nitrogen, oxygen and phosphorus).
    Method. Using a Monte Carlo code which has been developed to simulate the photoelectric effect on plasmid DNA pBR322, the energy deposition pattern of secondary electrons ejected after photoabsorption in DNA constituent atoms (not including the hydration shell) was calculated. Experimentally obtained X-ray absorption near edge structures were considered of the cross-sections at the K-shell resonant absorption (1s-->sigma*) of carbon, nitrogen and oxygen, and the K-shell resonant absorption (1s-->t2*) of phosphorus. Direct energy deposition by secondary electrons was scored using two different DNA models with and without the hydrated shell. The yields of SSB, DSB per photoabsorption events as well as break complexity were estimated for monochromatic X-rays around the K-edges of DNA constituent atoms (200-3000 eV).
    Results: Higher SSB and DSB yields were obtained below the carbon, nitrogen and oxygen K-edges compared to at or above the resonance, and at the K-shell resonant absorption of phosphorus compared to below the resonance. The number of electrons with sufficient energy to induce strand breaks was found to change depending on the photon energy. Electrons with 120 and 250 eV are shown to be rather more effective in SSB and DSB induction than electrons with higher energy. Inclusion of hydrated water in the DNA volume did not affect the photon energy dependence of the strand break yields.
    Conclusion: The small difference of photon energies around K-absorption edges of the carbon, nitrogen, oxygen and phosphorus is indicated to induce variation in strand break yields by direct effect. Higher SSB and DSB induction efficiencies could be due to a higher yield of more than two electrons with around 120 eV to 250 eV per photoabsorption event., INFORMA HEALTHCARE
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2004年11月, [査読有り]
  • "In situ" observation of guanine radicals induced by ultrasoft X-ray irradiation around the K-edge regions of nitrogen and oxygen
    A Yokoya; K Akamatsu; K Fujii; M Ukai, 筆頭著者, Purpose: In order to understand the molecular mechanism of nucleobase damage caused by ultrasoft X-ray irradiation, guanine radicals have been studied using an X-band EPR (electron paramagnetic resonance) spectrometer installed in a synchrotron soft X-ray beamline.
    Materials and Methods: Guanine pellets were irradiated under vacuum with ultrasoft X-rays obtained from a soft X-ray beamline (BL23SU) in SPring-8. The energy regions around the nitro en (0.4 keV) and oxygen (0.5 keV) K-edges were chosen for the irradiation. The ultrasoft X-ray irradiation and EPR measurements were carried out simultaneously at low temperature, 20 K and 77 K.
    Results: The EPR spectrum observed during irradiation was clearly distinguishable from that of the stable radical, which still exists after exposure to ultrasoft X-rays at 7 7 K. The spectrum of the short-lived radicals consisted of two components, which exhibited different EPR microwave power saturation. The EPR signal intensities increased linearly with increasing dose rate (photon flux density). These signals immediately disappeared when the beam was turned off, even when irradiated at lower temperature (20 K). At the energy of the oxygen K-resonance excitation (539 eV) the signal intensity was clearly increased to more than five times that obtained on the lower energy side (526 eV). On the other hand, the enhancement was insignificant above and below the nitrogen K-edge (401 eV). The singlet EPR signal of the stable radical was similar to that reported previously in the literature for gamma-irradiated guanine.
    Conclusions: The short-lived radical species observed were mainly induced as a result of the final state of the resonant Auger process oil oxygen atoms existing solely in the carbonyl group in guanine. Auger events at the other atoms in guanine (namely, carbon and nitrogen) do not induce this radical process to any great extent, even though the abundance of these atoms (i.e. the sum of their photoabsorption cross sections) is dominant in the guanine molecule., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2004年11月, [査読有り]
  • Low-energy Auger- and photo-electron effects on the degradation of thymine by ultrasoft X-irradiation
    K Akamatsu; K Fujii; A Yokoya, Purpose: To investigate quantitatively and qualitatively the production of thymine radicals produced by monochromatic ultrasoft X (USX) - or Co-60 gamma-rays using electron paramagnetic resonance (EPR) spectroscopy.
    Materials and Methods: Thymine was chosen as the DNA component for the irradiation. The EPR experiments of irradiated thymine were performed using an X-band EPR device installed in a soft X-ray beamline (BL23SU) in SPring-8. Sample pellets were irradiated with USX photons in a microwave cavity in a vacuum chamber. EPR measurements of thymine powder pellets irradiated with USX photons at energies of 407 and 538 eV were performed at 77 K or room temperature. For reference, Co-60 gamma-irradiation to a pellet was also performed at room temperature.
    Results: The following three features were found: 1) comparison between the two energies shows that the EPR dose-response curves are clearly distinguishable from each other: the curve for 407 eV saturated at a lower dose and spin number than that for 538 eV, 2) no evident qualitative difference between the radical species produced at the two energies was observed. 3) the EPR signal of the 538 eV USX-irradiated sample measured after annealing for 12 days is similar to that obtained with Co-70 gamma-irradiation.
    Conclusions: The difference observed in the EPR dose-response relationship reflects the difference in the K-absorption cross-sections of carbon, nitrogen and oxygen in the thymine molecule which govern the photo-/Auger electron energy spectrum., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2004年11月, [査読有り]
  • Decomposition of 2-deoxy-D-ribose by irradiation with 0.6 keV electrons and by 0.5 keV ultrasoft X-rays
    K Fujii; K Akamatsu; A Yokoya, Purpose: To compare the molecular decomposition of 2-deoxy-D-ribose induced by 0.6 keV electron irradiation or by 0.5 keV ultrasoft X-ray irradiation.Materials and methods: A thin film of 2-deoxy-D-ribose was irradiated by two radiation sources: low-energy (similar to 0.6 keV) electrons and ultrasoft X-rays (similar to 0.5 keV). The positive ions that were desorbed from the sample during the irradiation were measured using a quadrupole mass spectrometer. The spectral changes in the X-ray absorption near edge structure (XANES) were also examined after the irradiation.Results and discussion: The ions that were desorbed from 2-deoxy-D-ribose due to electron irradiation were mainly H+, CHx+, C2Hx+, CO+, CHxO+, C3Hx+, C2HxO+ and C-3,HxO+ (x= 1, 2, and 3) ions. These ions were the same as those observed in desorption due to ultrasoft X-ray irradiation. The XANES spectral changes induced by electron irradiation showed GO bond cleavage in the molecule and C = O bond formation in the surface residues. These results show that intensive molecular decomposition of the furanose ring structure was induced by both types of irradiation. It is inferred that these irradiation products are primarily produced by secondary electrons (several tens of eV), which are thought to be generated by both types of irradiation when they are applied to the 2-deoxy-D-ribose sample., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2004年11月, [査読有り]
  • 〔主要な業績〕EPR studies of 5-bromouracil crystal after irradiation with X rays in the bromine K-edge region
    A Yokoya; K Takakura; R Watanabe; K Akamatsu; T Ito, 筆頭著者, Radicals induced in a single crystal of 5-bromouracil (BrUra) by synchrotron soft X rays in the bromine K-edge region (13.461-13.482 keV) were investigated using the X-band EPR method. The crystal was irradiated at three peak energies of the absorption spectrum at room temperature or at 80 K. A hydrogen abstraction radical derived from N1 of the pyrimidine ring was commonly observed for all of the energies used, though with some variation in quantity. Similar characteristics were also observed in the EPR signal for the off-K-edge low-energy (13.42 keV) and (CO)-C-60 gamma rays used for comparison. When irradiated at 80 K, a much larger exposure (roughly 10 times) of soft X rays was needed to obtain the same signal intensity as that observed at room temperature. EPR signals were not detectable with gamma irradiation at liquid nitrogen temperature. (C) 2004 by Radiation Research Society., RADIATION RESEARCH SOC
    RADIATION RESEARCH, 2004年10月, [査読有り]
  • Near-edge X-ray absorption fine structure of DNA nucleobases thin film in the nitrogen and oxygen K-edge region
    K Fujii; K Akamatsu; A Yokoya, The near-edge X-ray absorption fine structure (NEXAFS) of evaporated thin films of DNA nucleobases on an Au-coated Si surface at room temperature has been investigated in the regions around the nitrogen and oxygen K-edges using highly monochromatic synchrotron soft X-rays. Each nucleobase shows a specific absorption spectrum originating from the resonant excitation of 1s electrons of nitrogen or oxygen to antibonding states, some of which strongly depend on the polarization angle of incident soft X-rays. From an analysis of the polarization angle dependences of the pi* resonance absorption intensity, it is found that purines are orientated to the multilayer surface with an angle of 15 +/- 6degrees for adenine and 38 +/- 1degrees for guanine. Uracil has an orientation of 16 +/- 4degrees, although other pyrimidines such as thymine and cytosine are randomly orientated with respect to the surface. These characteristics of the obtained NEXAFS spectra not only reveal the electrical structure of the nucleobases but also provide us with knowledge of the thermal stability of the self-organized base-stacking structure, which might play an important role in retaining the conformation of an intact or base-damaged DNA molecule., AMER CHEMICAL SOC
    JOURNAL OF PHYSICAL CHEMISTRY B, 2004年06月, [査読有り]
  • 〔主要な業績〕Ion desorption from DNA components irradiated with 0.5 keV ultrasoft X-ray photons
    K Fujii; K Akamatsu; A Yokoya, Positive ion desorption from thin films of DNA components, 2-deoxy-D-ribose, thymine, thymidine (dThd), and thymidine 5'-monophosphate (dTMP) was investigated in the oxygen K-shell edge excitation region using synchrotron ultrasoft X rays (538 eV). A large number of molecular fragments, H+, CHx+, C2Hx+, CO+, CHxO+, C3Hx+, C2HxO+ and C3HxO+ (x = 1, 2 and 3), were observed as desorbed ions from 2-deoxy-D-ribose. Some of these ions are related to simultaneous bond scission at particular C-C and C-O (or C-C) bonds in the furanose ring structure in the 2-deoxy-D-ribose molecule, indicating that the impact of photons on the oxygen atom and the impact of ejected secondary electrons (e.g. Auger electrons) cause an intense destruction of the furanose ring structure. In thymine thin films, H+, CHx+, CO+, CHxO+, C2HxN+ and CHxNO+ (x = 1, 2 and 3) fragments were observed. The yields of these ions were smaller than the yields from 2-deoxy-D-ribose. The desorption of CH3+ from thymine might induce a molecular conversion from thymine to uracil. The mass patterns of dThd and dTMP, and especially that of dTMP, were similar to that of 2-deoxy-D-ribose, indicating that a number of ions were generated at the sugar site, even in the nucleotide molecule. It is therefore predicted that the sugar moiety is more fragile than the thymine base. (C) 2004 by Radiation Research Society., RADIATION RESEARCH SOC
    RADIATION RESEARCH, 2004年04月, [査読有り]
  • Qualitative and quantitative analyses of the decomposition products that arise from the exposure of thymine to monochromatic ultrasoft X rays and Co-60 gamma rays in the solid state
    K Akamatsu; K Fujii; A Yokoya, HPLC analyses of condensed thymine irradiated with monochromatic synchrotron ultrasoft X rays in the energy region around nitrogen and oxygen K-shell edges were performed. Cobalt-60 gamma rays were used as a reference radiation. The radiation chemical dose response of each separated thymine decomposition product was also determined. Uracil (U), 5-(hydroxymethyl)uracil (HMU), 5,6-dihydrothymine (DHT), 5-formyluracil (foU) and four main unknown products were found in the HPLC chromatogram of the sample irradiated with ultrasoft X rays in vacuo. Similar spectra of the products were also found in the gamma-ray experiment; however, some unknown products that appeared after elution of the thymine peak were significantly larger than those in the ultrasoft Xray experiment. This result indicates the difference in radiation quality. The G value of DHT produced by gamma radiation was 10 times larger than those produced by the ultrasoft Xray photons with energies of 395 and 407 eV corresponding to below and on the nitrogen K-shell edge, respectively. This result suggests that the differences in the photon energy and/ or in the energy spectra of the secondary electron between ultrasoft X rays and gamma rays are causing differences in the process of the radiation chemistry. Moreover, the yields of all the thymine decomposition products induced by 538 eV photons (oxygen K-shell edge) were significantly smaller than those induced by photons around the nitrogen K-shell edge. The K-shell excitation of oxygen in thymine may efficiently promote the production of small thymine fragments susceptible to desorption from the sample. (C) 2004 by Radiation Research Society., RADIATION RESEARCH SOC
    RADIATION RESEARCH, 2004年04月, [査読有り]
  • The measurement of molecular fragments from DNA components using synchrotron radiation
    K Fujii; K Akamatsu; A Yokoya, Photon-stimulated desorption of positive ions from thin film DNA components, 2-deoxy-D-ribose, thymine and guanine, were investigated in the oxygen K-edge excitation region. H+, CH2+, C2H2+, CHO+, C3H3+ and CHO+ were desorbed mainly from the 2-deoxy-D-ribose thin film following oxygen K-edge excitation. The ion yields were obtained as a function of the photon energy. Each spectrum showed a prominent peak structure coinciding with the O1s --> sigma*(C-O) excitation energy. These results indicate that the observed ions are produced not only by direct photodecomposition but also by the impact of secondary electrons that the core excitation generates. On the other hand, H+ has been observed by irradiation of thymine and guanine thin films, while only insignificant amounts of the other ions were observed. It is shown that the core excitation more drastically degraded the 2-deoxy-D-ribose molecule into small fragments than is the case with the nucleobases. The sugar moiety in DNA is likely to be one of the nor fragile molecular sites, conducive to a single-strand DNA break. (C) 2002 Elsevier Science B.V. All rights reserved., ELSEVIER SCIENCE BV
    SURFACE SCIENCE, 2003年03月, [査読有り]
  • 〔主要な業績〕Effects of hydration on the induction of strand breaks, base lesions, and clustered damage in DNA films by alpha-radiation
    A Yokoya; SMT Cunniffe; DL Stevens; P O'Neill, 筆頭著者, The yields of DNA single (ssb)- and double-strand breaks (dsb) as well as base lesions, which are converted into detectable ssb by base excision repair enzymes, induced at 278 K by densely ionizing alpha-radiation have been determined as a function of the level of hydration (Gamma, number of water molecules per nucleoticle) of films of supercoiled plasmid DNA (pUC 18). The yields of prompt ssb induced by alpha-radiation are independent of Gamma, from vacuum-dried up to 35 water molecules per nucleotide, indicating that diffusible hydroxyl radicals or H2O.+, if induced in the hydrated layer by alpha-radiation, do not significantly contribute to the induction of ssb. In contrast, the yield of prompt dsb does increase with increasing hydration level. At a Gamma of 35, the yield of dsb is about twice that for gamma-irradiation. Treatment of alpha-particle-irradiated DNA with the enzymatic probes, endonuclease III (Nth), and formamidopyrimicline-DNA glycosylase (Fpg), does not lead to significant levels of additional ssb and dsb. It is proposed that (i) base lesions induced by direct energy deposition in the DNA-water complex by high LET radiation, such as cc-particles, are generally present in clustered DNA damage, e.g., two or more lesions produced within a few tens of base pairs, and (ii) the complexity of the clustered damage, lesion density, is greater for densely (compared with sparsely) ionizing radiation. As a consequence, the majority of DNA base lesions induced by high LET radiation, in contrast to those by low LET radiation, and which are substrates for Fpg and Nth become refractory to excision repair due to their formation within more complex, clustered DNA damage., AMER CHEMICAL SOC
    JOURNAL OF PHYSICAL CHEMISTRY B, 2003年01月, [査読有り]
  • X-ray absorption near edge structure of DNA bases around oxygen and nitrogen K-edge
    K Fujii; K Akamatsu; Y Muramatsu; A Yokoya, X-ray absorption near edge structure (XANES) spectra of DNA and the nucleobases (adenine, guanine, cytosine, thymine and uracil) are observed using monochromatic soft X-rays (400-560 eV). The photon energy range includes the electron binding energy of the core orbital of nitrogen and oxygen K shell. Obtained XANES spectra showing a characteristic structure were theoretically analyzed by the discrete variational density functional formalism (DV-Xalpha) method. These results clearly indicate that the photo-excitation of oxygen and nitrogen Is electron to pi* orbitals shows a sharp resonance profile rather than that to sigma* orbitals, enough to realize selecting a photochemical reaction site at specific nucleobases in a DNA molecule. Novel experiments are proposed based on the obtained spectra to understand the molecular mechanisms of radiation damages on DNA bases. (C) 2002 Elsevier Science B.V. All rights reserved., ELSEVIER SCIENCE BV
    NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS, 2003年01月, [査読有り]
  • Infrared spectral change in 2-deoxy-D-ribose by irradiation with monochromatic photons around oxygen K-edge
    K Akamatsu; K Fujii; A Yokoya, Analyses of chemical changes in DNA by energy deposition from ionizing radiation are quite important to strictly know characteristics of radiobiological effects. Monochromatic photons from synchrotron radiation are one of the powerful probes to investigate the effects. As a step for the aim, chemical analyses by Fourier-transform infrared spectroscopy of the samples irradiated with the monochromatic photons were performed. It appeared that 2-deoxy-D-ribose irradiated around the energy of oxygen K-edge contained C=O or C=C, which would be responsible for a direct strand break of DNA. These data are noteworthy to find not only the strand scission at 2-deoxy-D-ribose moiety by the direct energy deposition by photon but also the following radiobiological responses such as cell killing or mutation. (C) 2002 Elsevier Science B.V. All rights reserved., ELSEVIER SCIENCE BV
    NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS, 2003年01月, [査読有り]
  • 〔主要な業績〕Electron paramagnetic resonance induced by K-shell resonance excitation in DNA bases in solid state
    A Yokoya; K Akamatsu; K Fujii, 筆頭著者, DNA base radicals were examined around oxygen K-edge region using an EPR spectrometer installed in a synchrotron soft X-ray beamline (BL23SU) in SPring-8. In situ measurements of EPR spectrum of guanine and thymine revealed that short-lived transient radical species are induced by photoexcitation of O 1s electron to sigma* orbital. They promptly disappear by "beam-off". On the other hand, long-lived radicals whose EPR spectra are consistent with previous reports for guanine cation and thymine anion radical are accumulated during the irradiation. These results indicate that chemically stable DNA base lesions, such as 8-oxo-G, would result from transient species that are inferred to be one electron oxidized radicals after decay of Auger final state. (C) 2002 Elsevier Science B.V. All rights reserved., ELSEVIER SCIENCE BV
    NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS, 2003年01月, [査読有り]
  • 〔主要な業績〕Effect of hydration on the induction of strand breaks and base lesions in plasmid DNA films by gamma-radiation
    A Yokoya; SMT Cunniffe; P O'Neill, 筆頭著者, The yields of gamma-radiation-induced single- and double-strand breaks (ssb's and dsb's) as well as base lesions, which are converted into detectable ssb by the base excision repair enzymes endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg), at 278 K have been measured as a function of the level of hydration of closed-circular plasmid DNA (pUC18) films. The yields of ssb and dsb increase slightly on increasing the level of hydration (Gamma) from vacuum-dried DNA up to DNA containing 15 mol of water per mole of nucleotide. At higher levels of hydration (15 < Gamma < 35), the yields are constant, indicating that H2O.+ or diffusible hydroxyl radicals, if produced in the hydrated layer, do not contribute significantly to the induction of strand breaks. In contrast, the yields of base lesions, recognized by Nth and Fpg, increase with increasing hydration of the DNA over the range studied. The maximum ratios of the yields of base lesions to that of ssb are 1.7:1 and 1.4:1 for Nth- and Fpg-sensitive sites, respectively. The yields of additional dsb, revealed after enzymatic treatment, increase with increasing level of hydration of DNA. The maximum yield of these enzymatically induced dsb is almost the same as that for prompt, radiation-induced dsb's, indicating that certain types of enzymatically revealed, clustered DNA damage, e.g., two or more lesions closely located, one on each DNA strand, are induced in hydrated DNA by radiation. It is proposed that direct energy deposition in the hydration layer of DNA produces H2O.+ and an electron, which react with DNA to produce mainly base lesions but not ssb. The nucleobases are oxidized by H2O.+ in competition with its conversion to hydroxyl radicals, which if formed do not produce ssb's, presumably due to their scavenging by Tris present in the samples. This pathway plays an important role in the induction of base lesions and clustered DNA damage by direct energy deposition in hydrated DNA and is important in understanding the processes that lead to radiation degradation of DNA in cells or biological samples., AMER CHEMICAL SOC
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002年07月, [査読有り]
  • First results from the actinide science beamline BL23SU at SPring-8
    Y Saitoh; T Nakatani; T Matsushita; A Agui; A Yoshigoe; Y Teraoka; A Yokoya, The present performance of a soft X-ray beamline BL23SU at SPring-8 is described. The resolving power realized on a varied-line-spacing plane grating monochromator connected to a variably polarizing undulator was estimated to be better than 10 000 at 400 eV and similar to 6500 at 867 eV. In addition, reasonable photon flux of more than 10(11) photons/s/100 mA/0.02% b.w. is available in the energy range of 0.5-1.8 keV at experimental stations. (C) 2001 Elsevier Science B.V. All rights reserved., ELSEVIER SCIENCE BV
    NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT, 2001年12月, [査読有り]
  • Reparability of lethal lesions produced by phosphorus photoabsorption in yeast cells
    N Usami; A Yokoya; S Ishizaka; K Kobayashi, The characteristics of DNA lesions produced by the photoabsorption of phosphorus in yeast cells were studied using monochromatized soft X-rays tuned to the absorption peak of the phosphorus K-edge (2153 eV) and below the peak energy (2147 eV). The repaired fractions of DNA double-strand breaks (dsb) were measured relatively by using both a mutant, rad 54-3, which shows the temperature-sensitive dsb repair-deficient phenotype, and a wild-type strain. The repaired fraction of lesion in rad 54-3, which corresponds to the relative yield of dsb reparable by the RAD 54 pathway, was not affected by the phosphorus photo absorption. Repair of the produced lesions in the wild-type cells was also measured by comparing the surviving fraction of the immediately plated cells to that of those cells plated after holding in a non-nutrient medium for 80 hrs. The recovery of the surviving fraction after the holding treatment was dependent upon the irradiated X-ray energy. These results suggest that irreparable lesions are produced by the inner-shell photoabsorption of phosphorus in DNA, although its yield is small., JAPAN RADIATION RESEARCH SOC
    JOURNAL OF RADIATION RESEARCH, 2001年09月, [査読有り]
  • First operation of circular dichroism measurements with periodic photon-helicity switching by a variably polarizing undulator at BL23SU at SPring-8
    A Agui; A Yoshigoe; T Nakatani; T Matsushita; Y Saitoh; A Yokoya; H Tanaka; Y Miyahara; T Shimada; M Takeuchi; T Bizen; S Sasaki; M Takao; H Aoyagi; TP Kudo; K Satoh; S Wu; Y Hiramatsu; H Ohkuma, This article presents the first operation of the magnetic circular dichroism (MCD) measurement system with periodic photon-helicity switching. The measurements were performed at the newly constructed soft x-ray beamline-BL23SU- at the third-generation synchrotron radiation facility, SPring-8. The monochromator control system was synchronized to the movement of the magnetic row (phase shift) of an APPLE-2 (Sasaki) type variably polarizing undulator. The periodic phase shift of the undulator provided the switching of helicity polarizing soft x rays up to 0.1 Hz. The closed-orbit distortion of the storage ring was controlled to avoid optical axis disturbances at this beamline as well as at other beamlines. The circular dichroism spectra with helicity switching by APPLE-2 show the possibility of high-sensitivity MCD measurements. This method promotes precise MCD measurements and can be a powerful technique to study magnetism as well as dichroism. (C) 2001 American Institute of Physics., AMER INST PHYSICS
    REVIEW OF SCIENTIFIC INSTRUMENTS, 2001年08月, [査読有り]
  • Synchronous beam diagnostic system using cordless telephones at SPring-8
    TP Kudo; H Aoyagi; K Sato; S Wu; H Tanaka; S Sasaki; T Nakatani; M Takeuchi; T Shimada; Y Hiramatsu; A Yokoya; A Agui; A Yoshigoe; H Ohkuma; Y Miyahara; T Ishikawa; H Kitamura, Recently, we have developed a synchronous SR beam position diagnostic system. In this system, more than one X-ray beam position monitor is used synchronously and an oscillation of the SR beam position all through the storage ring can be detected. For an example, during the high speed driving of the insertion device, beam oscillation and shift can be simultaneously observed at different beamlines. To start the measurements simultaneously at the different beamlines, a trigger signal was conveyed by a cordless telephone. This paper describes the system and performance tests of it. (C) 2001 Elsevier Science B.V. All rights reserved., ELSEVIER SCIENCE BV
    NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT, 2001年07月, [査読有り]
  • EPR spectrometer installed in a soft X-ray beamline at SPring-8 for biophysical studies
    A Yokoya; K Akamatsu, 筆頭著者, We have developed an Electron paramagnetic resonance (EPR) system combined with a synchrotron beamline (Synchrotron Light Excited Electron Paramagnetic Resonance Spectrometer (SLEEPRS)) to detect radicals in biomolecules caused by irradiating with soft X-rays below 2keV. SLEEPRS was installed in a soft X-ray undulator beamline equipped with a grazing incidence grating monochromator (BL23SU, SPring-8). The cavity of the X-band microwave was set in a high vacuum chamber connected with the beamline transport channel. The sample temperature was controlled from 10 to 300 K by a closed-cycle cryogenic system during the soft X-ray irradiation and the EPR measurements. Typical EPR signals of a deaminated alanine radical from L-a-alanine were observed by irradiating 1.5 keV soft X-rays, The calculated absorbed dose shows that a dose of the same order or less gives the same EPR signal intensity as that generated by a conventional 100 kVp X-ray source. Thus the combination of an EPR spectrometer and synchrotron soft X-ray beamline may open a way for investigating the radical processes involved in biomolecular damages induced by a selective K-photoabsorption of a specific atom. (C), 2001 Elsevier Science B.V. All rights reserved., ELSEVIER SCIENCE BV
    NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT, 2001年07月, [査読有り]
  • X-ray absorption near-edge structure (XANES) spectral changes of 2-deoxy-D-ribose by irradiation within the energy region around the oxygen K-shell absorption edge
    K Akamatsu; A Yokoya, The physicochemical characteristics of 2-deoxy-D-ribose moieties in DNA strands are important to understand biological radiation stress. So, the X-ray absorption near edge structure (XANES) of 2-deoxy-D-ribose within the energy region around the oxygen K-shell absorption edge was measured. 2-deoxy-D-ribose was exposed to 3 energies of X-rays, i.e., 526.3 eV (below O 1s-->pi*), 537.8 eV (at the absorption peak of O 1s-->sigma*) and 552.6 eV (above O 1s-->sigma*) for given periods. Slight differences in spectral changes were seen in the each irradiation energy, suggesting in fact that the chemical state and following rearranged chemical structure of 2-deoxy-D-ribose may be different between the 3 irradiation energies., MUNKSGAARD INT PUBL LTD
    JOURNAL OF SYNCHROTRON RADIATION, 2001年03月, [査読有り]
  • A grating monochromator of BL23SU at SPring-8 covering silicon and oxygen K-edges
    A Yoshigoe; A Agui; T Nakatani; T Matsusita; Y Saitoh; A Yokoya, We report the present performance of a grating monochromator at the newly constructed soft x-ray beamline (BL23SU at the SPring-8), which can measure both silicon and oxygen K-edges. That provides new opportunities for XAFS measurements of solids up to 2100 eV., MUNKSGAARD INT PUBL LTD
    JOURNAL OF SYNCHROTRON RADIATION, 2001年03月, [査読有り]
  • X-ray absorption near edge structures of DNA or its components around the oxygen K-shell edge
    K Akamatsu; A Yokoya, The initial process of radiation damage in DNA was investigated by measuring the X-ray absorption near edge structures (XANES) within the energy region around the oxygen K-shell absorption edge for DNA, cytosine and 2-deoxy-D-ribose. Irradiation and XANES experiments were performed with the BL23SU soft X-ray beamline, using synchrotron radiation from the 8 GeV electron storage ring at SPring-8. Samples were mounted on gold-coated plates in a vacuum chamber. The XANES spectra were obtained by measuring the photoelectron current of the samples. 2-Deoxy-D-ribose was exposed to X rays at the absorption peak corresponding to the oxygen (O) 1s-->sigma* transition energy (538 eV); the XANES spectra were obtained after each irradiation. DNA and cytosine, possessing characteristic XANES spectra, both had two major energy bands corresponding to the O 1s-->pi* and 1s-->sigma* transitions, Two new peaks appeared and gradually increased in the XANES spectra of 2-deoxy-D-ribose during irradiation. These results suggest that C-O bonds in 2-deoxy-D-ribose are transformed to C=O bonds by O 1s-->sigma* transition, suggesting that the molecules undergo chemical changes into carbonyl-containing compounds. (C) 2001 By Radiation Research Society., RADIATION RESEARCH SOC
    RADIATION RESEARCH, 2001年03月, [査読有り]
  • Photoionization of Ne3+ ions in the region of the 1s -> 2p autoionizing resonance
    M Oura; H Yamaoka; K Kawatsura; J Kimata; T Hayaishi; T Takahashi; T Koizumi; T Sekioka; M Terasawa; Y Itoh; Y Awaya; A Yokoya; A Agui; A Yoshigoe; Y Saitoh, Photoion yields of Ne4+ from Ne3+ ions were successfully measured in the region of the 1s --> 2p autoionizing resonance by a photon-ion mer ed-beam technique. A broad structure centered at 864.5 eV, which is composed of several transitions, was observed in the photoion-yield spectrum. The spectrum was analyzed with the results of multiconfiguration Dirac-Fock calculations. The calculations revealed that the lines contained in the broad structure can be attributed to possible transitions from the 2s(2)2p(3) S-4(3/2), D-2(3/2) and D-2(5/2) initial levels. The calculated spectrum satisfactorily shows an overall agreement with the experimental one., AMERICAN PHYSICAL SOC
    PHYSICAL REVIEW A, 2001年01月, [査読有り]
  • 酸素K殻領域でのアミノ酸蒸着膜のNEXAFS測定
    田中真人; 古結俊行; 児玉洋子; 横谷明徳; 安居院あかね; 赤松憲; 中川和道, Oxygen K-edge X-ray absorption near edge structures (XANES) spectra of amino acids (glycine, L-alpha -alanine, beta -alanine, L-serine, L-asparic acid and L-tyrosine) were measured. Several peaks of XANES spectra were successfully assigned on the basis of DV-X alpha calculation., MUNKSGAARD INT PUBL LTD
    放射線化学討論会講演要旨集, 2000年, [査読有り]
  • 〔主要な業績〕Single- and double-strand breaks in solid pBR322 DNA induced by ultrasoft X-rays at photon energies of 388, 435 and 573 eV
    A Yokoya; R Watanabe; T Hara, 筆頭著者, We measured strand breaks of pBR322 plasmid DNA irradiated with ultrasoft X-rays using monochromatic synchrotron radiation as a light source. Three photon energies, 388, 435 and 573 eV, a value below and above the nitrogen K-edge and above the oxygen K-edge, respectively, were chosen for the irradiation experiments as they have an equivalent photon transmittance of the sample. Irradiated DNA was analyzed by agarose gel electrophoresis and the numbers of single-and double-strand breaks (ssb and dsb) were determined by measuring the band intensity on the gel after ethidium bromide staining. The action cross-sections for the ssb and dsb slightly increased with the photon energy. The ratio between 388 and 573 eV was about 1.5 for both forms of strand breaks. The absorbed energy required far a strand break was about 60 eV for ssb and 1 keV for dsb, less than one fifth of the values obtained previously in the 2 keV region. On the other hand, the absorbed energies per strand break, as well as the ratio of the action cross-section for the ssb to that for the dsb, were constant regardless of the photon energy used. The K-shell photoabsorption on carbon, nitrogen and oxygen atoms in the DNA molecule, followed by an Auger cascade, induced DNA strand breaks with a constant efficiency in terms of the absorbed energy. These results indicate that the strand breaks of the DNA molecule in the solid state are mainly caused by the photo- and Auger-electrons and the efficiency of the strand breaks little depends on the atoms ejecting these secondary electrons., JAPAN RADIATION RESEARCH SOC
    JOURNAL OF RADIATION RESEARCH, 1999年06月, [査読有り]
  • Construction of the JAERI soft X-ray beamline for actinide material sciences
    T Nakatani; Y Saitoh; Y Teraoka; T Okane; A Yokoya, An undulator beamline for spectroscopy studies focusing on the electronic structure of actinide materials is under construction. Linearly or circularly polarized soft X-rays are provided by employing a variably polarizing undulator. Varied-line-spacing plane gratings and a sagittal-focusing system are used to monochromatize the undulator beam, whose energy ranges from 0.3 to 1.5 keV. A resolving power of 10(4) is expected in the whole energy region. These components are methodically operated by the SPring-8 beamline control system. There are three experimental stations in the beamline. In one of the stations the photoemission spectroscopy experiments are carried out at a radioisotope-controlled area where actinide compounds as well as unsealed radioactive materials are usable. Other experimental stations are planned in the beamline for surface photochemical reactions and biological applications., MUNKSGAARD INT PUBL LTD
    JOURNAL OF SYNCHROTRON RADIATION, 1998年05月, [査読有り]
  • 〔主要な業績〕Soft X-ray beamline specialized for actinides and radioactive materials equipped with a variably polarizing undulator
    A Yokoya; T Sekiguchi; Y Saitoh; T Okane; T Nakatani; T Shimada; H Kobayashi; M Takao; Y Teraoka; Y Hayashi; S Sasaki; Y Miyahara; T Harami; TA Sasaki, 筆頭著者, This report presents the design of an undulator beamline at SPring-s to be used for soft X-ray spectroscopy focused on radioactive materials. Photoemission spectroscopy experiments are carried out in a radioisotope (RI)-controlled area where actinide compounds as well as unsealed radioactive materials are usable. Intrusion of the radioactive materials into the electron storage ring or to the outside of the evacuated beamline components can be avoided by a specially devised RI protection/inspection mechanism. The combination of a variably polarizing undulator and a varied-line-spacing plane-grating monochromator provides linearly or circularly polarized soft X-rays with a high resolving power in the energy range 0.28-1.5 keV. The beamline will become operational in December 1997., MUNKSGAARD INT PUBL LTD
    JOURNAL OF SYNCHROTRON RADIATION, 1998年01月, [査読有り]
  • Single- and double-strand breaks in pBR322 plasmid DNA by monochromatic X-rays on and off the K-absorption peak of phosphorus
    K Hieda; T Hirono; A Azami; M Suzuki; Y Furusawa; H Maezawa; N Usami; A Yokoya; K Kobayashi, Using a synchrotron irradiation system pBR322 plasmid DNA was irradiated under vacuum by monochromatic X-rays having five specific photon energies (2.147, 2.153, 2.159, 2.168 and 2.199 KeV) both on and off the It-absorption peak (2.153 keV) of phosphorus. The single-and double-strand breaks (ssb and dsb) were measured as conversions of the closed circular form of DNA (form I) to open circular (form II) and linear (form III) forms respectively. Exposures to induce one strand break per molecule were lowest at the peak (2.153 keV), and highest at 2.147 KeV; the ratios were 2.7 for ssb and 3.0 for dsb. The exposures for dsb were 21-26 times higher than those for ssb. When the exposures were converted to absorbed doses in grays the absorbed doses per ssb were almost independent of photon energy. This result indicates that a certain absorbed dose was necessary to induce a ssb, regardless of whether photons were absorbed by the It-shell of phosphorus or by other shells, or by other atoms. However, the absorbed dose per dsb at 2.147 keV was 1.17 times higher than that averaged over four X-ray energies above 2.153 keV, indicating that the Ii-shell absorption, and the subsequent Auger event, efficiently induce dsb. The results are also discussed concerning the number of photo-absorptions of the constituent atoms pel DNA strand break., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1996年10月, [査読有り]
  • Synchrotron radiation beamline to study radioactive materials at the photon factory
    H Konishi; A Yokoya; H Shiwaku; H Motohashi; T Makita; Y Kashihara; S Hashimoto; T Harami; TA Sasaki; H Maeta; H Ohno; H Maezawa; S Asaoka; N Kanaya; K Ito; N Usami; K Kobayashi, Design and construction of a new beamline have been described. The beamline is housed in a specially designed area controlled for radioactive materials at the Photon Factory (PF) in the National Laboratory for High Energy Physics (KEK). The beamline system consists of a front-end and two branchlines. One of the branchlines is used for X-ray photoelectron spectroscopy and radiation biology in the energy range of 1.8-6 keV and the other for X-ray diffractometry and XAFS studies as well as radiation biology in the range of 4-20 keV. The former was particularly equipped for the protection against accidental scattering of radioactive materials both inside and outside of the vacuum system., ELSEVIER SCIENCE BV
    NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT, 1996年03月, [査読有り]
  • Lethal effect of K-shell absorption of intracellular phosphorus on wild-type and radiation sensitive mutants of Escherichia coli
    H Maezawa; Y Furusawa; K Kobayashi; K Hieda; M Suzuki; N Usami; A Yokoya; T Mori, The present study was conducted to clarify the lethality of Auger cascades induced by the K-shell photoabsorption of phosphorus in Escherichia coli. Killing of wild-type and radiation-sensitive mutants of E. coli was examined. Three x-ray energies were chosen for irradiation; at 2.153 keV: the resonance peak of K-shell photoabsorption of phosphorus; at 2.146 and 2.160 keV: off-peak. Enhancement ratio, which was defined as the ratio of the killing sensitivity of 2.153 keV to that at 2.146 keV, were 1.32 to 1.54 for examined strains. Increment of absorbed energy calculated in entire cells for 2.153 keV radiation could not explain the degree of observed enhancement of killing. Lethality of Anger cascades depended on the killing sensitivity with x-rays which did not induce Auger cascades. The lethality for wild-type was lower than that for recombination repair-deficient mutants. It was concluded that one part of damages produced by Auger cascades was repaired in wild-type strains., SCANDINAVIAN UNIVERSITY PRESS
    ACTA ONCOLOGICA, 1996年, [査読有り]
  • INACTIVATION ACTION SPECTRA OF BACILLUS-SUBTILIS SPORES WITH MONOCHROMATIC SOFT X-RAYS (0.1-0.6 NM) OF SYNCHROTRON RADIATION
    N MUNAKATA; K HIEDA; N USAMI; A YOKOYA; K KOBAYASHI, RADIATION RESEARCH SOC
    RADIATION RESEARCH, 1992年07月, [査読有り]
  • MUTAGENIC AND TRANSFORMING EFFECTS OF SOFT-X-RAYS WITH RESONANCE ENERGY OF PHOSPHORUS K-ABSORPTION EDGE
    M WATANABE; M SUZUKI; K WATANABE; K SUZUKI; N USAMI; A YOKOYA; K KOBAYASHI, Syrian golden hamster embryo (SHE) cells were exposed to synchrotron-produced monochromatic X-rays at 5.747 (2.159 keV), 5.763 (2.153 keV) and 5.779 angstrom (2.147 keV). Although X-rays of all wavelengths induced mutations and chromatid aberrations in a dose-dependent manner, when cells were irradiated with 2.153 keV X-rays, which correspond to the resonance energy of the phosphorus K-absorption edge, the frequencies of mutation and chromatid aberration at equal dose levels were higher than for X-rays of the other wavelengths. At equal survival levels, however, there was no difference in the frequencies of mutations and chromatid aberrations in cells irradiated with soft X-rays. On the other hand, the frequency of morphological transformation in cells irradiated with 2.147 keV X-rays was higher than those irradiated with 2.153 keV and 2.159 keV X-rays. The relative biological effectiveness compared to cobalt-60 gamma-rays in morphological transformation was 2.8 for 2.147 keV, 1.1 for 2.159 keV and 1.0 for 2.153 keV at a 37% survival level., TAYLOR & FRANCIS LTD
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1992年02月, [査読有り]
  • RADIOLYTIC DEGRADATION OF CYSTATHIONINE IRRADIATED WITH MONOCHROMATIC SOFT X-RAYS AT THE K-SHELL RESONANCE-ABSORPTION OF SULFUR
    A YOKOYA; K KOBAYASHI; N USAMI; S ISHIZAKA, 筆頭著者, The degradation of cystathionine was investigated using irradiation with monochromatized synchrotron X-rays at 2472 eV and 2466 eV. 2472 eV corresponds to the energy of the K-shell resonance absorption peak of the sulfur atom. The energy at 2466 eV was adopted as a reference. Cystathionine has a sulfur atom which joins two amino acid residues. This form is useful for analyzing the effect of degradation that originates from photoexcitation in the sulfur atom. The degradation products of cystathionine were detected by high performance liquid chromatography (HPLC). Of the products present, alpha-aminobutyric acid was produced threefold on irradiation with 2472 eV X-rays, as compared with the value for irradiation at 2466 eV and the same exposure. Almost the same amount of glycine was produced at the two irradiation energies. The yields of these two products were analyzed on the basis of the amount of cystathionine degraded and the number of photons absorbed by sulfur and the other elements in cystathionine. Cleavage of a bond was shown to depend on whether the bond includes an atom that absorbs the X-ray photon., JAPAN RADIATION RESEARCH SOC
    JOURNAL OF RADIATION RESEARCH, 1991年06月, [査読有り]
  • TARGET SIZE FOR A FIBRONECTIN-CELL ADHESION SYSTEM DETERMINED BY THE X-RAY INACTIVATION METHOD
    A YOKOYA; K KOBAYASHI; Y MIYAMOTO; S ISHIZAKA, 筆頭著者, In order to elucidate the mechanism of cell adhesion, the size of the functional site, both in the fibronectin molecule and in the mouse fibroblast cell, responsible for cell adhesion activity, was determined. The size was assumed to be equivalent to the target size, that can be determined from the X-ray inactivation dose. The target size of the cell-binding site in the fibronectin molecule was 32 kdalton. The molecular weight was much larger than that of the tripeptide, which has been reported to be the minimum peptides having a cell-binding activity. This suggests that submolecular regions in fibronectin other than the tripeptide are necessary for cell adhesion. The target size in the cell responsible for the adhesion to the fibronectin-coated surface was 4300 kdalton. The large molecular weight of the target could be explained by assuming that a complex protein system is involved in the cell-adhesion process in the cell., JAPAN SOC CELL BIOLOGY
    CELL STRUCTURE AND FUNCTION, 1991年02月, [査読有り]
  • INTERACTION BETWEEN CELL-BINDING DOMAIN AND EXTRACELLULAR MATRIX-BINDING DOMAIN OF FIBRONECTIN DETERMINED BY FLUORESCENCE DEPOLARIZATION
    Y MIYAMOTO; A YOKOYA; S ISHIZAKA, ELSEVIER SCIENCE BV
    BIOCHIMICA ET BIOPHYSICA ACTA, 1988年04月, [査読有り]

MISC

書籍等出版物

  • 2-6.放射線ストレスに対する量子効果に基づくゲノム安定化機構の解明               
    横谷 明徳; 藤井 健太郎, 分担執筆
    高エネルギー加速器研究機構・放射光科学研究施設, 2016年10月31日
  • Spectroscopic study of radiation-induced DNA lesions and their susceptibility to enzymatic repair
    Akinari Yokoya; Kentaro Fujii; Naoya Shikazono; Masatoshi Ukai, 共著
    CRC Press, 2010年01月01日, [査読有り]

講演・口頭発表等

  • 放射線影響の初期過程から細胞応答のシステム的統合理解に向けて               
    横谷明徳
    令和5年東京RBC新春放談会, 2023年02月04日, [招待有り]
    20230204, 20230204
  • 2ビーム利用による新しいサイエンス (放射線生物UG)               
    横谷 明徳
    PF研究会「開発研究多機能ビームラインの建設と利用」②, 2023年01月05日, [招待有り]
    20230105, 20230106
  • DNA repair response of mammary gland cells to EGFP plasmid DNA exposed to various ionizing radiations or treated with restriction enzymes               
    Yui Obata; Akari Kinase; Keishiro Hirasaki; Nobuyoshi Akimitsu; Akinari Yokoy
    68th Annual International Meeting of Radiation Research Society, 2022年10月17日
    20221016, 20221019
  • Structural change in DNA repair protein XRCC4 by multimerization revealed by CD and SAXS               
    Kai Nishikubo; Maho Hasegawa; Yoshihisa Matsumoto; Akinari Yokoy
    68th Annual International Meeting of Radiation Research Society, 2022年10月17日
    20221016, 20221019
  • 電子状態の物理学的理解による放射線生体分子変異プロセスの探索
    横谷 明徳
    日本放射線影響学会第65回大会, 2022年09月16日, [招待有り]
    20220915, 20220917
  • クラスターDNA損傷               
    横谷 明徳
    Auger Therapy 研究会, 2022年09月05日, [招待有り]
    20220905, 20220905
  • Exploring active structures of DNA repair protein XRCC4 using CD and SAXS
    横谷明徳; 西久保開; 長谷川真保
    The 26th Hiroshima International Symposium on Synchrotron Radiation, 2022年02月18日, [招待有り]
    20220217, 20220218
  • 放射線誘発DNA初期損傷に対する添加剤の化学修復効果               
    于暠; 藤井健太郎; 横谷明徳; 山下真一
    日本放射線影響学会第64回大会, 2021年09月23日, [招待有り]
    20210922, 20210924
  • 放射線、生命科学、そして物理学
    横谷明徳
    日本放射線影響学会第64回大会, 2021年09月23日, [招待有り]
    20210922, 20210924
  • X線マイクロビームの可変ジオメトリックパターンと細胞・細胞集団ターゲティン グ
    横谷明徳
    日本放射線影響学会若手部会第1回総会・日本マイクロビーム生物研究会第11回連絡会議(総会)・高LET研究会, 2020年10月14日, [招待有り]
    20201014, 20201014
  • 薬剤及び放射線ストレスによる動物培養細胞内のミトコンドリア動態と ATP産生の変化               
    木村由佳; 大内則幸; 鈴木啓司; 横谷明徳
    第13回Quantum Medicine研究会(茨城大学理学部公開シンポジウム), 2020年02月23日, [招待有り]
    20200223, 20200223
  • Do bromine atoms incorporated into DNA obscure the photon-induced Auger effect on damage induction?               
    Akinari Yokoya
    The 9th International Symposium on Physical, Molecular, Cellular, and Medical Aspects of Auger Processes, 2019年08月23日, [招待有り]
    20190822, 20190824
  • Fluorescent Nanodiamonds for Intracellular Measurements               
    Ryuji Igarashi; Kiichi Kaminaga; Daiki Terada; Takahiro Fujisaku; Takuya Genjo; Takuya F. Segawa; Akinari Yokoya; Masahiro Shirakawa
    PhotonIcs & Electromagnetics Research Symposium also known as Progress In Electromagnetics Research Symposium (PIERS 2019), 2019年06月17日, [招待有り]
    20190617, 20190620
  • Quantum Tools to Explore Radiobiological Effects on Living Systems
    Akinari Yokoya
    PhotonIcs & Electromagnetics Research Symposium also known as Progress In Electromagnetics Research Symposium (PIERS 2019), 2019年06月17日, [招待有り]
    20190617, 20190620
  • In vitro 照射プラスミドをトランスフェクションした細胞のライブセル観察               
    小畑結衣; 横谷明徳
    第12回 Quantum Medicine 研究会(茨城大学理学部 公開シンポジウム ), 2019年02月17日, [招待有り]
    20190217, 20190217
  • マイクロビームX線照射後のミトコンドリア活性変化のライブセル観察               
    横谷明徳; 神長輝一; 浜田涼; 宇佐美徳子; 鈴木啓司
    若⼿放射線⽣物学研究会 平成 30 年度専⾨研究会, 2018年09月01日, [招待有り]
    20180901, 20180902
  • 放射光を量子ツールとして用いた生命・医科学研究               
    横谷 明徳
    JAEA-QST放射光科学シンポジウム2018, 2018年03月12日, [招待有り]
    20180312, 20180314
  • 放射線による複雑なDNA損傷の生成に 関する物理化学的初期過程の研究               
    横谷 明徳
    長崎原研研究会, 2018年02月28日, [招待有り]
    20180228, 20180228
  • Development of the ex vivo spermatogenesis technique for advanced radiotherapeutic science               
    Hisanori Fukunaga; Kiichi Kaminaga; Takuya Sato; Karl T. Butterworth; Akinari Yokoya; Takehiko Ogawa; Kevin M. Prise
    2017年度生命科学系学会合同年次大会 (ConBio2017), 2017年11月30日, [招待有り]
    20171128, 20171130
  • Synchrotron Radiation as a Quantum Tool for Studies of Radiation Damage to DNA and Resulting Cellular Responses               
    横谷 明徳; 藤井 健太郎; 島田 紘行; 鵜飼 正敏; 神長輝一; 大和田 謙二; 町田 晃彦; 今岡 達彦; 西村 由希子
    2017年度生命科学系学会合同年次大会 (ConBio2017), 2017年11月29日, [招待有り]
    20171128, 20171130
  • Novel analytical study for reaction intermediates in the primary radiation interaction of DNA using a synchrotron radiation induced luminescence spectroscopy               
    T.Kojima; H.Aihara; Y.Kodashima; H.Makishima; S.Nakiri; S.Takada; H.Shimada; C.Ozga; X.Holzapfel; Ph.Schimid; C.Küstner-Wetekamm; H.Otto; A.Knie; A.Ehresmann; A.Yokoya; K.Fujii; Y.Fukuda; M.Ukai
    17th International Symposium on Microdosimetry (MICROS 2017), 2017年11月07日
    20171105, 20171110
  • Visualization of DNA Repair Process in Mammalian Cells Transformed by Plasmid DNA Exposed to X-rays in vitro               
    Hiroki Nakaue; Yui Obata; Kiichi Kaminaga; Akinari Yokoy
    17th International Symposium on Microdosimetry (MICROS2017), 2017年11月07日
    20171105, 20171110
  • ハロゲン化ピリミジンを含むDNA の放射線増感の電子物性の研究               
    鬼澤 美智; 芳賀 芳範; 田中 成典; 鯉渕 誠也; 横谷 明徳
    第60回 日本放射線影響学会大会, 2017年10月28日, [招待有り]
    20171025, 20171028
  • X線マイクロビーム照射後のミトコンドリア活性の変化               
    横谷 明徳; 神長 輝一; 浜田 涼; 宇佐美 徳子; 鈴木 啓司
    第60回 日本放射線影響学会大会, 2017年10月26日, [招待有り]
    20171025, 20171028
  • 水中でエネルギー付与された電子の動的挙動               
    甲斐健師; 樋川智洋; 鵜飼正敏; 藤井健太郎; 渡邊立子; 横谷明徳
    第60回放射化学討論会, 2017年09月28日, [招待有り]
    20170927, 20170929
  • Fragmentation of Doubly-Ionized Deoxyribose. Ab Initio Molecular Dynamics Simulations               
    Marie Anne Hervé du Penhoa; Alexandre Souchaud; Rodolphe Vuilleumier; Ivano Tavernelli; Marie Pierre Gaigeo; Kentaro Fujii; Akinari Yokoya; Marie Françoise Politis
    The first International Symposium of QST - Quantum Life Sciences -, 2017年07月25日, [招待有り]
    20170725, 20170726
  • High Brilliance Synchrotron Radiation as a Tool for Studies of Radiation Damage to DNA and resulting cellular responses               
    Akinari Yokoya
    The first International Symposium of QST - Quantum Life Sciences -, 2017年07月25日, [招待有り]
    20170725, 20170726
  • Live imaging of cells exposed to ionizing radiation               
    Akinari Yokoya; Kiichi Kaminaga; Tatsuhiko Imaoka; Takeshi Ohshima; Ryuji Igarashi
    QUANTUM SENSING IN BIOLOGY WORKSHOP in University of Melbourne, 2017年03月28日, [招待有り]
    20170328, 20170328
  • X線マイクロビーム照射後の細胞運命とミトコンドリア活性変化               
    横谷 明徳; 神長 輝一; 濱田 涼; 宇佐美 徳子; 鈴木 啓司
    第10回Quantum Medicine研究会(茨城大学理学部公開シンポジウム), 2017年02月12日, [招待有り]
    20170212, 20170212
  • Various modes of DNA damage formation by the direct effect of radiation               
    横谷 明徳
    The 56th Annual Meeting of Radiation Research Society, 2010年09月25日, [招待有り]

所属学協会

  • 2012年04月 - 現在, PFユーザーアソシエーション
  • 量子生命科学研究会
  • 日本放射線化学会
  • 日本放射線影響学会
  • 日本放射光学会

共同研究・競争的資金等の研究課題