Evaluation of SCCVII tumor cell survival in clamped and non-clamped solid tumors exposed to carbon-ion beams in comparison to X-rays

Hirayama, Ryoichi*; Uzawa, Akiko*; Takase, Nobuhiro*; Matsumoto, Yoshitaka*; Noguchi, Miho; Koda, Kana*; Ozaki, Masakuni*; Yamashita, Kei*; Li, H.*; Kase, Yuki*; et al.

Mutation Research; Genetic Toxicology And Environmental Mutagenesis, 756(1-2), p.146 - 151, 2013/08

https://doi.org/10.1016/j.mrgentox.2013.05.008

Full-coherent HHG-seeded EUV-FEL locked by EOS timing feedback

Ogawa, Kanade*; Sato, Takahiro*; Matsubara, Shinichi*; Okayasu, Yuichi*; Togashi, Tadashi*; Watanabe, Takahiro*; Takahashi, Eiji*; Midorikawa, Katsumi*; Aoyama, Makoto; Yamakawa, Koichi; et al.

Proceedings of 10th Conference on Lasers and Electro-Optics Pacific Rim and 18th OptoElectronics and Communications Conference and Photonics in Switching 2013 (CLEO-PR & OECC/PS 2013) (USB Flash Drive), 2 Pages, 2013/06

https://doi.org/10.1109/CLEOPR.2013.6600178

no abstracts in English

The First electron bunch measurement by means of dast organic EO crystals

Okayasu, Yuichi*; Tomizawa, Hiromitsu*; Matsubara, Shinichi*; Sato, Takahiro*; Ogawa, Kanade*; Togashi, Tadashi*; Takahashi, Eiji*; Minamide, Hiroaki*; Matsukawa, Ken*; Aoyama, Makoto; et al.

Proceedings of 1st International Beam Instrumentation Conference (IBIC 2012) (Internet), 5 Pages, 2012/10

http://accelconf.web.cern.ch/Accelconf/IBIC2012/talks/mocc03_talk.pdf

no abstracts in English

Induction of DNA DSB and its rejoining in clamped and non-clamped tumours after exposure to carbon ion beams in comparison to X-rays

Hirayama, Ryoichi*; Uzawa, Akiko*; Matsumoto, Yoshitaka*; Noguchi, Miho; Kase, Yuki*; Takase, Nobuhiro*; Ito, Atsushi*; Koike, Sachiko*; Ando, Koichi*; Okayasu, Ryuichi*; et al.

Radiation Protection Dosimetry, 143(2-4), p.508 - 512, 2011/02

https://doi.org/10.1093/rpd/ncq478

We studied double-strand breaks (DSB) induction and rejoining in clamped and non-clamped transplanted tumours in mice leg after exposure to 80 keV/m carbon ions and X-rays. The yields of DSB in the tumours were analysed by a static-field gel electrophoresis. The OER of DSB after X-rays was 1.68, and this value was not changed after 1 h rejoining time (1.40). These damages in oxygenated conditions were rejoined 60-70% within 1 h in situ. No difference was found between the exposure to X-rays and carbon ions for the induction and rejoining of DSB. Thus, the values of OER and rejoined fraction after exposure to carbon ions were similar to those after X-rays, and the calculated relative biological effectivenesses of carbon ion were around 1 under both oxygen conditions. The yields of DSB in vivo depend on exposure doses, oxygen conditions and rejoining time, but not on the types of radiation quality.

Enhanced radiation-induced cell killing by Herbimycin A pre-treatment

Noguchi, Miho; Hirayama, Ryoichi*; Druzhinin, S.*; Okayasu, Ryuichi*

Radiation Physics and Chemistry, 78(12), p.1184 - 1187, 2009/12

https://doi.org/10.1016/j.radphyschem.2009.07.008

Herbimycin A (HA), as in Geldanamycin, binds to conserved pockets of heat shock protein 90 (Hsp90) and inhibits its chaperone functions. Hsp90 plays an integral role in cancer cell growth and survival, because it maintains the stability of several key proteins by its chaperone's activity. It is known that some of the proteins associated with radiation responses are functionally stabilized by Hsp90. In this study, we investigated the effect of HA on radiosensitivity in human cancer cells and the mechanism related to the sensitization. In order to gain a mechanistic insight of this sensitization, we examined repair of DNA double strand breaks (DSBs) in irradiated human cancer cells pre-treated with HA, as unrepaired DSBs are thought to be the main cause of radiation-induced cell death. Cellular radiosensitivity was determined by clonogenic assay, and the DSB rejoining kinetics was examined by constant field gel electrophoresis. SQ-5, a lung squamous carcinoma cell line, showed synergistic increase in radiosensitivity when cells were pre-treated with HA. In addition, HA significantly inhibited repair of radiation induced DSBs. These results suggest that the combination of HA and ionizing radiation may be a useful therapeutic strategy for treating certain cancer cells.

Contributions of direct and indirect actions in cell killing by high-LET radiations

Hirayama, Ryoichi*; Ito, Atsushi*; Tomita, Masanori*; Tsukada, Teruyo*; Yatagai, Fumio*; Noguchi, Miho; Matsumoto, Yoshitaka*; Kase, Yuki*; Ando, Koichi*; Okayasu, Ryuichi*; et al.

Radiation Research, 171(2), p.212 - 218, 2009/02

https://doi.org/10.1667/RR1490.1

The biological effects of radiation originate principally in damages to DNA. DNA damages by X-rays as well as heavy ions are induced by a combination of direct and indirect actions. The contribution of indirect action in cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide (DMSO), which suppresses indirect action without affecting direct action. Exponentially growing Chinese hamster V79 cells were exposed to high-LET radiations of 20 to 2106 keV/m in the presence or absence of DMSO and their survival was determined using a colony formation assay. The contribution of indirect action to cell killing decreased with increasing LET. However, the contribution did not reach zero even at very high LETs and was estimated to be 32% at an LET of 2106 keV/m. Therefore, even though the radiochemically estimated G value of OH radicals was nearly zero at an LET of 1000 keV/m, indirect action by OH radicals contributed to a substantial fraction of the biological effects of high-LET radiations. The RBE determined at a survival level of 10% increased with LET, reaching a maximum value of 2.88 at 200 keV/m, and decreased thereafter. When the RBE was estimated separately for direct action (RBE(D)) and indirect action (RBE(I)); both exhibited an LET dependence similar to that of the RBE, peaking at 200 keV/m. However, the peak value was much higher for RBE(D) (5.99) than RBE(I) (1.89). Thus direct action contributes more to the high RBE of high-LET radiations than indirect action does.

17-allylamino-17-demethoxygeldanamycin enhances the cytotoxicity of tumor cells irradiated with carbon ions

Noguchi, Miho; Hirayama, Ryoichi*; Okayasu, Ryuichi*

no journal, , 

We investigated radiosensitization effect and its mechanism of Hsp90 inhibitor 17-AAG in human tumor cell lines irradiated with high LET carbon ions. Human tumor cell lines, DU145 derived from prostate carcinoma and normal human fibroblasts HFL III were incubated for 24 h in the presence of 17-AAG at concentration of 100nM. The cells were then irradiated with carbon ions (290MeV/nucleon, LET70keV/um) and several biological endpoints were compared. Cellular radiation sensitivity was determined by clonogenic assay and DNA double strand break (DSB) repair kinetics were examined by constant field gel electrophoresis. DU145 cells showed an increase in carbon ions-induced cell death when pre-treated with 17-AAG. The radiosensitivity enhancement ratios measured at a survival rate of 10% were 2.13 for DU145 cells. In contrast to the tumor cell lines, normal human fibroblasts with carbon irradiation showed no radiosensitization with 17-AAG pre-treatment. Our constant field gel electrophoresis studies indicated that 17-AAG had almost no effect on carbon ion-induced DSB repair in DU145 cells. On the other hand, radiation induced Rad51 foci formation showed different kinetics between the carbon ion alone and the combined treatment with 17-AAG and carbon ions in DU145 cells. Our findings suggest that mechanisms other than inhibition of DSB repair could be involved with the radiosensitization by 17-AAG in tumor cells irradiated with carbon ions. However, limited inhibition of homologous recombination by this agent may still be a possibility.

Stable operation of HHG-seeded EUV-FEL at the SCSS test accelerator

Tomizawa, Hiromitsu*; Hara, Toru*; Ishikawa, Tetsuya*; Ogawa, Kanade*; Tanaka, Hitoshi*; Tanaka, Takatsugu*; Togashi, Tadashi*; Togawa, Kazuaki*; Yabashi, Makina*; Aoyama, Makoto; et al.

no journal, , 

no abstracts in English

Sustained lasing of HHG-seeded FEL by using EOS-based timing control

Watanabe, Takahiro*; Aoyama, Makoto; Iwasaki, Atsushi*; Otake, Yuji*; Oshima, Takashi*; Okayasu, Yuichi*; Ogawa, Kanade*; Owada, Shigeki*; Sato, Takahiro*; Togashi, Tadashi*; et al.

no journal, , 

no abstracts in English

Enhanced radiation induced cell killing by Herbimycin A pre-treatment

Noguchi, Miho; Hirayama, Ryoichi*; Druzhinin, S.*; Okayasu, Ryuichi*

no journal, , 

Herbimycin A binds to conserved pockets of heat shock protein 90 (Hsp90) and inhibits its chaperone functions. Hsp90 plays an important role in tumor cell growth and survival though maintaining stability of proteins by its chaperone activity. It is known that some of the proteins associated with radio-resistance are functionally stabilized on Hsp90. In this study, we investigated the effect of herbimycin A on radiation sensitivity in human tumor cells and the mechanism related to the sensitization. For mechanistic insight, we examined repair of DNA double strand breaks (DSBs) in irradiated human cells pre-treated with herbimycin A. The lung squamous carcinoma cell cine, SQ-5, was used. Cells were treated with 1, 2, and 4 M herbimycin A for 24 h before X-irradiation. SQ-5 cells showed increased radiation sensitivity when pre-treated with herbimycin A. In addition, herbimycin A significantly inhibited repair of radiation induced DSBs. It is possible that one of the proteins associated with DNA DSB repair might be degraded by this drug as previously shown with another Hsp90 inhibitor 17-AAG, a geldanamycin derivative.