Development of bio-dosimetry for the evaluation of low dose radiation and carcinogenic risk estimation
Project/Area Number |
17310036
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Risk sciences of radiation/Chemicals
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Research Institution | Hiroshima University |
Principal Investigator |
KAMIYA Kenji Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor (60116564)
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Co-Investigator(Kenkyū-buntansha) |
MASUDA Yuji Hiroshima University, Research Institute for Radiation Biology and Medicine, Assistant Professor (30273866)
TOYOSHIMA Megumi Hiroshima University, Research Institute for Radiation Biology and Medicine, Assistant Professor (80423052)
神谷 研二 広島大学, 原爆放射線医科学研究所, 教授 (60116564)
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Project Period (FY) |
2005 – 2007
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Project Status |
Completed (Fiscal Year 2007)
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Budget Amount *help |
¥16,970,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2006: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2005: ¥5,700,000 (Direct Cost: ¥5,700,000)
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Keywords | Reyl / genome damage / DNA repair / translesion DNA synthesis / Double strand break / Radiation / Histnne H2AX / Bio-dosimetry / REV1 / ゲノム修復 / ポリメラーゼ / 突然変異 |
Research Abstract |
We have tried to develop the hypersensitive mouse model and molecular bio-dosimery using DNA damage response proteins based on these functional analyses for the estimation of carcinogenic risk and dose after radiation exposure. 1. Development of hypersensitive monitor mouse for the estimation of low-dose radiation exposure and analysis of its biological character The Y-family DNA polymerases play roles for maintenance of genetic stability. Malfunction of the polymerases affect cancer susceptibility. Revl, the number of the Y-family DNA polymerase, has deoxycytidyl transferase activity and plays the central role on the translesion DNA synthesis known as error-prone DNA repair. In order to develop hypersensitive model mouse for radiation exposure, we have generated Levi transgenic mice (Rev1 mouse). Therefore Levi mouse showed increased susceptibility to tumorigenesis after carcinogenic insult, we analyzed the biological character of this mouse. Furthermore, to determine how increasing .RE
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V1 affects the biological phenotype of cells, human fibrosarcoma cells were transfected with hREV1 expression plasmid having tetracycline regulation system and then the stable sublines were isolated. We found that the cells expressing hREV1 were resistant to the cytotoxic effect of X-ray irradiation more than parental cells. This observation suggests the survived cells may increase the accumulation of mutations after the repair process of damaged DNA. 2. Research on the development of molecular bio-dosimery for low dose radiation In order to develop new molecular bio-dosimery, we have focused our research on functional analysis of protein complex on damaged site of genome including Histone H2AX and REV1 complex which are visualized as foci and countable in cell nucleus. We have detected the possible candidate molecules for the molecular bio-dosimery. We found DNA damage-dependent modification of H2AX enhances chromatin dynamics. We also succeeded in analysis of translesion DNA sythesis on the reconstituteion system. Less
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Report
(4 results)
Research Products
(180 results)
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[Presentation] (*Department of Biology, Faculty of Sciences, Kyushu Univ.) : Dynamics of human replication factors2007
Author(s)
Masuda, Y., Suzuki, M., Piao, J.L., Gu, Y.Q., Tsurimoto, T., Kamiya, K
Organizer
The 79th Annual Meeting of the Genetics Society of Japan
Place of Presentation
Okayama
Year and Date
2007-09-19
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] (*Department of Biology, Faculty of Sciences, Kyushu Univ.) Dynamic properties of human replication factors in the elongation of DNA replication2007
Author(s)
Masuda, Y., Suzuki, M., Piao, J.L., Gu, Y.Q., Tsurimoto, T., Kamiya, K
Organizer
CSHL Meeting-Eukaryotic DNA Replication & Genome Maintenance
Place of Presentation
New York
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] 放射線発がんのメカニズム2005
Author(s)
神谷研二
Organizer
第46回原子爆弾後障害研究会
Place of Presentation
広島
Year and Date
2005-06-04
Description
「研究成果報告書概要(和文)」より
Related Report
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