Development of bio-dosimetry for the evaluation of low dose radiation and carcinogenic risk estimation

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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 characterThe 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 … More 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 radiationIn 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