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Journal Articles

Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

Tomita, Masanori*; Matsumoto, Hideki*; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke*; Maeda, Munetoshi*; Kobayashi, Yasuhiko

Life Sciences in Space Research, 6, p.36 - 43, 2015/07

A radiation-induced bystander response is generally known as a cellular response induced in unirradiated cell by receiving bystander signaling factors released from directly irradiated cells of a cell population. Bystander responses induced by high-LET heavy ions at low fluence are an important problem concerning the health of astronauts in the space environment. Here we set out NO-mediated bystander signal transductions induced by high-LET heavy-ion microbeam irradiation in normal human fibroblasts. Our findings suggest that Akt- and NF-$$kappa$$B-dependent signaling pathway involving COX-2 plays an important role in the NO-mediated high-LET heavy-ion-induced bystander responses. Additionally, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells, which are distinguish form directly irradiated cells.

Journal Articles

Mechanisms for the induction of radioadaptive response by radiation-induced bystander response

Matsumoto, Hideki*; Tomita, Masanori*; Otsuka, Kensuke*; Hatashita, Masanori*; Maeda, Munetoshi*; Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Sakashita, Tetsuya; Ikeda, Hiroko; et al.

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 76, 2015/03

The objective of this project is to elucidate molecular mechanisms for the induction of radioadaptive response through radiation-induced bystander responses induced by irradiation with heavy ion microbeams in JAEA. We found that the adaptive response was induced by Ar (520 MeV $$^{40}$$Ar$$^{14+}$$) microbeam-irradiation of a limited number of cells, followed by the broad beam-irradiation and that the adaptive response was almost completely suppressed by the addition of carboxy-PTIO, as a nitric oxide (NO) scavenger. In addition, we found several genes induced specifically and preferentially when radioadaptive response could be induced. We confirmed that ${it iNOS}$ expression was specifically induced only when radioadaptive response could be induced. Our findings strongly suggested that radioadaptive response can be induced by NO-mediated bystander responses evoked by irradiation with heavy ion microbeams.

Journal Articles

Analysis of bystander response in 3D cultured tissue induced by heavy-ion microbeam irradiation

Tomita, Masanori*; Matsumoto, Hideki*; Otsuka, Kensuke*; Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 77, 2015/03

Radiation-induced bystander responses are defined as responses in cells that have not been directly targeted by radiation but are in the neighborhood of cells that have been directly exposed. In this study, we aim to clarify a role of bystander response to sustain the homeostasis of damaged tissue using heavy-ion microbeams. We established the heavy-ion microbeam irradiation method to a 3D cultured human epidermis. Using this method, a viable cell rate of the 3D cultured human epidermis irradiated with 260 MeV $$^{20}$$Ne-ion microbeams or broadbeams was analyzed by the MTT method.

Journal Articles

Microbeam irradiation facilities for radiobiology in Japan and China

Kobayashi, Yasuhiko; Funayama, Tomoo; Hamada, Nobuyuki*; Sakashita, Tetsuya; Konishi, Teruaki*; Imaseki, Hitoshi*; Yasuda, Keisuke*; Hatashita, Masanori*; Takagi, Keiichi*; Hatori, Satoshi*; et al.

Journal of Radiation Research, 50(Suppl.A), p.A29 - A47, 2009/03

 Times Cited Count:37 Percentile:72.85(Biology)

Journal Articles

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

 Times Cited Count:112 Percentile:95.48(Biology)

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/$$mu$$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/$$mu$$m. Therefore, even though the radiochemically estimated G value of OH radicals was nearly zero at an LET of 1000 keV/$$mu$$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/$$mu$$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/$$mu$$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.

Oral presentation

What are the mediators of bystander response induced by irradiation of argon particles?

Matsumoto, Hideki*; Tomita, Masanori*; Otsuka, Kensuke*; Funayama, Tomoo; Kobayashi, Yasuhiko

no journal, , 

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