2003 Fiscal Year Final Research Report Summary
Role of DNA double-strand break repair on low dose rate effects
| Project/Area Number |
14380250
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
UTSUMI Hiroshi KYOTO UNIVERSITY RESEARCH REACTOR INSTITUTE, PRPFESSOR, 原子炉実験所, 教授 (20025646)
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| Co-Investigator(Kenkyū-buntansha) |
TACHIBANA Akira KYOTO UNIVERSITY RADIATION RESEARCH CENTER, ASSOCIAATE PROFESSOR, 放射線生物研究センター, 助教授 (20188262)
YASUHIRA Shinji KYOTO UNIVERSITY RESEARCH REACTOR INSTITUTE, ASSOCIATE RESEARCHER, 原子炉実験所, 助手 (90311729)
TANO Keizou KYOTO UNIVERSITY RESEARCH REACTOR INSTITUTE, ASSOCIATE PRPFESSOR, 原子炉実験所, 助教授 (00183468)
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| Project Period (FY) |
2002 – 2003
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| Keywords | knockout mutant / DNA double-strand break / homologous recombination / non-homologous end-joining / sublethal damage repair / low dose rate effects |
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| Research Abstract |
It has been generally accepted that low dose rate effects (LDRE) results from, the sublethal damage (SLD) repair/split-dose recovery. As the dose rate is lowered and the treatment time protracted, more and more SLD can be repaired during the exposure. Recently we found that SLD repair due to DSB repair mediated by homologous recombination (HR) repair. To study the molecular mechanism of LDRE, we analyzed the knock-out mutants KU70^<-/->, RAD54^<-/->, and KU70^<-/->/RAD54^<-/-> of the chicken B-cell line, DT40. Rad54 participates in the HR repair of DSBs, while Ku proteins are involved in NHEJ. Survival enhancement by LDR irradiation was observed in parent DT40 and RAD54^<-/-> cells but not in non-homologous end joining (NHEJ) deficient KU70^<-/-> and KU70^<-/->/RAD54^<-/-> cells. In the LDRE, NHEJ pathway was more important than HR pathway. This suggests that LDRE are not directly attributable to the SLD repair because the SLD repair results from the HR pathway of DSBs. Under continuous LDR irradiation, dividing chicken cells can progress through the cell cycle. Since NHEJ-deficient cells will be killed in G1 phase, NHEJ pathway plays an important role in LDRE.
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[Publications] Y.Yasud, Y.Fujita, T.Matsuo, S.Koinuma, S.Hara, A.Tazaki, M.Onozaki, M.Hashimoto, T.Musha, K.Ogawa, H.Fujita, Y.Nakamura, H.Shiozaki, H.Utsumi: "Erythropoietin regulates tumor growth of human malignancies."Carcinogenesis. 124. 1021-1029 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Y.Simada, M.Nishmura, S.Kakinuma, T.Ogiu, H.Fujimoto, A.Kubo, J.Nagai, K.Kobayashi, K.Tano, S.Yoshinaga, K.K.Bhakat: "Genetic susceptibility to thymic lymphomas, and K-rays gene mutation in mice after exposure to X-rays and N-ethyl-N-nitrosourea."INT.J.RADIAT.BIOL.. 79(6). 423-430 (2003)
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「研究成果報告書概要(欧文)」より
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