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Takahashi, Akihisa*; Kubo, Makoto*; Igarashi, Chie*; Yoshida, Yukari*; Funayama, Tomoo; Kobayashi, Yasuhiko; Nakano, Takashi*
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 82, 2015/03
DNA double-strand breaks (DSBs) induced by ionizing radiation pose a major threat to cell survival. The cell can respond to the presence of DSBs, through two major repair pathways: Homologous recombination (HR) and non-homologous end-joining (NHEJ). Higher levels of cell death are induced by high-LET radiation when compared to low-LET radiation, even at the same doses because of less effective or more inefficient DNA repair. In this study, we examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Wild-type cells and HR deficient (but NHEJ proficient) cells exhibited the high RBE values at LET values of 108 keV/
m. The RBE value for each cell type decreased with increasing LET values over 200 keV/m. Although NHEJ proficient cells had an almost constant SER value, NHEJ deficient cells showed a high SER value when compared to NHEJ proficient cells, even with increasing LET values.
Takahashi, Akihisa*; Kubo, Makoto*; Ma, H.*; Nakagawa, Akiko*; Yoshida, Yukari*; Isono, Mayu*; Kanai, Tatsuaki*; Ono, Tatsuya*; Furusawa, Yoshiya*; Funayama, Tomoo; et al.
Radiation Research, 182(3), p.338 - 344, 2014/09
Times Cited Count：57 Percentile：90.66(Biology)To clarify whether high-LET radiation inhibits all repair pathways or specifically one repair pathway, studies were designed to examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Embryonic fibroblasts bearing repair gene KO were exposed to X rays, carbon-, iron-, neon- and argon-ion beams. Cell survival was measured with colony-forming assays. The sensitization enhancement ratio (SER) values were calculated using the 10% survival dose of wild-type cells and repair-deficient cells. Cellular radiosensitivity was listed in descending order: double-KO cells 
NHEJ-KO cells HR-KO cells wild-type cells. Although HR-KO cells had an almost constant SER value, NHEJ-KO cells showed a high-SER value when compared to HR-KO cells, even with increasing LET values. These results suggest that with carbon-ion therapy, targeting NHEJ repair yields higher radiosensitivity than targeting homologous recombination repair.
Murata, Kazutoshi*; Noda, Shinei*; Oike, Takahiro*; Takahashi, Akihisa*; Yoshida, Yukari*; Suzuki, Yoshiyuki*; Ono, Tatsuya*; Funayama, Tomoo; Kobayashi, Yasuhiko; Takahashi, Takeo*; et al.
Journal of Radiation Research, 55(4), p.658 - 664, 2014/07
Times Cited Count：16 Percentile：55.86(Biology)The effect of carbon ion irradiation on cell motility through the Rho signaling pathway in the human lung adenocarcinoma cell line A549 was studied. At 48 h after irradiation, the cell motility of A549 cells became significantly greater, and the formation of protrusions significantly increased in cells irradiated with carbon ion. The observed increase in cell motility due to carbon ion irradiation was similar to that observed due to X-ray irradiation. Western-blot analysis showed that carbon ion irradiation increased P-MLC2-S19 expression compared with in unirradiated controls, while total MLC2 expression was unchanged. Exposure to a non-toxic concentration of Y-27632, a specific inhibitor of ROCK, reduced the expression of P-MLC2-S19 after C-ion irradiation, resulting in a significant reduction in migration. These data suggest that carbon irradiation increases cell motility in A549 cells via the Rho signaling pathway and that ROCK inhibition reduces that effect.
Hamada, Nobuyuki*; Imaoka, Tatsuhiko*; Masunaga, Shinichiro*; Ogata, Toshiyuki*; Okayasu, Ryuichi*; Takahashi, Akihisa*; Kato, Takamitsu*; Kobayashi, Yasuhiko; Onishi, Takeo*; Ono, Koji*; et al.
Journal of Radiation Research, 51(4), p.365 - 383, 2010/07
Times Cited Count：115 Percentile：91.16(Biology)Matsumoto, Hideki*; Hamada, Nobuyuki*; Takahashi, Akihisa*; Kobayashi, Yasuhiko; Onishi, Takeo*
Journal of Radiation Research, 48(2), p.97 - 106, 2007/03
Times Cited Count：122 Percentile：90.34(Biology)The risks of low dose ionizing irradiation (
100 mSv) have been estimated using a linear no-threshold model by extrapolating from data obtained after high dose irradiation. The validity of this dose-response model is, however, controversial because evidence accumulated for over the past decade has shown that response of living organisms including humans to low dose/low dose-rate radiation is different from that to high dose/high dose-rate radiation. In another words, findings that cannot be explained by the classical "target theory" of radiobiology have accumulated. The radiation-induced adaptive response, bystander effects, low-dose radio-hypersensitivity, and genomic instability are specifically observed in response to low dose/low dose-rate radiation, and underpinnings of these responses often involve biochemical/molecular signals responding to targeted and non-targeted events. Recently, interrelations between the radioadaptive and bystander responses have been increasingly reported. We review observations supporting the existence of the latter two phenomena, and discuss the possible link between them from the aspect of production of reactive oxygen and nitrogen species.
Matsumoto, Hideki*; Hatashita, Masanori*; Takahashi, Akihisa*; Hamada, Nobuyuki*; Wada, Seiichi*; Funayama, Tomoo; Sakashita, Tetsuya; Kakizaki, Takehiko; Kobayashi, Yasuhiko
JAEA-Review 2006-042, JAEA Takasaki Annual Report 2005, P. 111, 2007/02
Matsumoto, Hideki*; Hatashita, Masanori*; Takahashi, Akihisa*; Hamada, Nobuyuki*; Wada, Seiichi*; Kobayashi, Yasuhiko; Funayama, Tomoo; Sakashita, Tetsuya; Kakizaki, Takehiko
no journal, ,
no abstracts in English
Murata, Kazutoshi*; Noda, Shinei*; Oike, Takahiro*; Takahashi, Akihisa*; Yoshida, Yukari*; Suzuki, Yoshiyuki*; Ono, Tatsuya*; Funayama, Tomoo; Kobayashi, Yasuhiko; Takahashi, Takeo*; et al.
no journal, ,
This study aimed to investigate the effect of carbon ion (C-ion) irradiation on cell motility through the ras homolog gene family member (Rho) signaling pathway in the human lung adenocarcinoma cell line A549. Cell motility was assessed by a wound-healing assay, and the formation of cell protrusions was evaluated by F-actin staining. Cell viability was examined by the WST-1 assay. The expression of myosin light chain 2 (MLC2) and the phosphorylation of MLC2 at Ser19 (P MLC2-S19) were analyzed by Western blot. The data suggest that C-ion irradiation increases cell motility in A549 cells via the Rho signaling pathway and that ROCK inhibition reduces that effect.
