| Project/Area Number |
11680549
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KAMIYA Kenji Research Institute for Radiation Biology and Medicine, Hiroshima University, Professor, 原爆放射能医学研究所, 教授 (60116564)
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| Co-Investigator(Kenkyū-buntansha) |
IKURA Tsuyoshi Research Institute for Radiation Biology and Medicine, Hiroshima University, Research Associate, 原爆放射能医学研究所, 助手 (70335686)
SUMII Masaharu Faculty of Medicine, Hiroshima University, Research Associate, 医学部, 助手 (60284220)
MASUDA Yuji Research Institute for Radiation Biology and Medicine, Hiroshima University, Research Associate, 原爆放射能医学研究所, 助手 (30273866)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | CRAD / REV1 / Sdf211 / hepatoma / error-prone DNA repair / mutation / androgen / endreticulum stress / 放射線 / 遺伝子損傷 / 遺伝子発現 / translesion DNA合成 / 放射線発がん / SDF2L1 / 小胞体蛋白 / ストレス蛋白 / DNA修復 / 損傷乗り越えDNA複製 / マウス肝癌 / 放射線誘発肝癌 / 肝癌細胞株 / CRAD1 / CRAD2 / CRAD3 |
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| Research Abstract |
To clarify the molecular mechanism of radiation-carcinogenesis, and apply it to the risk estimation, we conducted two experiments. Firstly, we analyzed the expression of genes in radiation-induced-mouse hepatomas. Mouse hepatomas were induced in B6C3F1 mice by 3Gy of ^<60>Coγ-ray exposure, and mRNAs were isolated from hepatomas and normal liver in the same mice. We identified differentially expressed genes by differential display technique. We found nineteen differentially expressed genes in hepatomas. Expressions of five genes were decreased and those of other fourteen genes were increase in hepatomas, including novel three genes named CRAD3 that was a member of cis-retinol/androgen dehydrogenase (CRAD) family, Sdf211 that was a member of Pmt/rt family, and A141-36 whose homology was not identified. CRAD plays an important role in androgen metabolism, which converts inactive 3α-adiol, into active dihydrotestosterone, (oxidative 3α-hydroxysteroid dehydrogenase activities : oxidative 3α
… More
-HSD activities) and consequently increases androgen activity. Actually, oxidative 3α-HSD activity in mouse hepatomas was found to be higher than that in normal liver at physiological 3α-adiol level. Dihydrotestosterone is well known to promote hepatocarcinogenesis. Therefore, the over-expression of CRAD3 must modify the radiation-induced mouse hepatocarcinogenesis by increasing local dihydrotestosterone level. Secondly, we try to clarify the involvement of spontaneous mutations in radiation carcinogenesis, because similarity of mutation spectra between radiation-induced and spontaneous cancers was well documented. We characterized mouse and human Revl gene which was a member of the UmuC/DinB/XPV gene family, played important roles in spontaneous mutations. Biochemical analysis of the mouse Rev1 protein revealed that the mouse Rev1 protein possessed a deoxycytidyl transferase activity as human REV1 protein. The expression of mouse Rev1 gene of primary embryonic fibroblasts in culture was induced by radiation exposure. This observation might be important, because the biochemical property suggested that the activity of the Rev1 protein was required for bypassing oxidative DNA damage by translesioh DNA synthesis during DNA replication. Less
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