| Project/Area Number |
09680528
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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 | Nagasaki University |
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Principal Investigator |
OKAICHI Kumio Nagasaki University, School of Medicine, Associate Professor, 医学部, 助教授 (80124874)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Yutaka Nagasaki University, School of Medicine, Professor, 医学部, 教授 (00073130)
井原 誠 長崎大学, 医学部, 助手 (60175213)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | p53 / mutation / radio-sensitivity / signal transduction / apoptosis / transduction / Saos2 / 変異部位 / シグナル伝達 / G1停止 / SaOS-2 |
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| Research Abstract |
We have constructed an in vitro system to examine how p53 mutants affect radiosensitivity. Mutations of p53 were made using in vitro mutagenesis, and mutant cDNAs were introduced into the human osteosarcoma cell line, Saos-2, which is devoid of endogenous p53. For wild type p53, both the expression plasmid and a regulation plasmid (LacSwitch system) were transfected into the cells. The radiosensitivities of clones of mutant p53 and wild type p53 were examined. Transformants of wild type p53 had increased radiosensitivity. A mutation at codon 123 also increased radiosensitivity. Mutations at codons 143, 175, and 273 did not alter radiosensitivity. The 123A point mutation of p53 was detected as a wild type in the yeast functional assay. The 123A mutant accumulated p53 in response to IR. The 123A mutant did not induced p21 but normally responded MDM2, Bax and Bcl-2. The 123A mutant entered apoptosis earlier than the wild type p53 transformant and induced Fas at early time in response to IR.
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