| Project/Area Number |
09680519
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
TACHIBANA Akira Kyoto University, Radiation Biology Center, Instractor, 放射線生物研究センター, 助手 (20188262)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Masao Kyoto University, Radiation Biology Center, Professor, 放射線生物研究センター, 教授 (20013857)
EJIMA Yosuke Kyoto University, Radiation Biology Center, Associate Professor, 放射線生物研究センター, 助教授 (50127057)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | radioadaptive response / repair of double-strand breaks in DNA / cellular signal transduction / p53 gene / protein kinase C / MAP kinase / non-homologous end-joining |
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| Research Abstract |
Eukaryotic cells are known to have an adaptive response that enhances radioresistance after a low priming dose of radiation. This radioadaptive response seems to present a novel cellular defense mechanism. We studied the role of protein kinase C(PKC) and mitogen-activated protein kinase (MAPK) in the expression of radioadaptive response in cultured mouse cells. PKC-a was activated immediately after X-irradiation. Low dose X-rays also activated the p38 MAPK. The activation of p38 MAPK and resistance to chromosome aberration formation were blocked by SB203580, an inhibitor of p38 MAPK, and Calphostin C, an inhibitor of PKC. Our results indicate the presence of a novel mechanism for coordinated regulation of adaptive response to low-dose X-rays by a nexus of PKC-a/p38 MAPK feedback signaling pathway. We also analyzed the end-joining reaction of double-strand breaks in DNA using in vitro system with nuclear extracts from cells exposed to X-rays, as the double-strand break(dsb)in DNA has be
… More
en implicated as the critical lesion induced by ionizing radiation leading to chromosome aberrations, mutations and cell death. The efficiency of end-joining by the extract from preexposed cells challenged with 3Gy after incubation for 5 hours (2cGy+3Gy extract) was higher than that by the extract from cells exposed to 3Gy X-rays (3Gy extract). The fidelity or end-joining was also estimated from the frequency of mutant plasmids. Although the end-joining fidelities of the 3Gy extract and the extract from unirradiated cells were comparable, the fidelity of the 2cGy+3Gy extract was much higher than these. We further examined the junction sequences in the recovered plasmid DNA with mis-rejoining of double-strand breaks. All mis-rejoined plasmids contained deletions missing at least several nucleotides from the break point to both sides. Short direct repeats of several nucleotides were found at all junction points. No significant differences were observed among the repeat sequences by the unirradiated extract, 3Gy extract and 2cGy+3Gy extract. The sizes of deletions by the 2cGy+3Gy extract tended to be smaller than these by the 3Gy extract Less
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