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 for the estimation of carcinogenic risk and dose after radiation exposure.1.Development of hypersensitive mouse model for radiation exposureRev1 protein belongs to a family of translesion DNA polymerases. Rev1 is responsible for error-prone translesion synthesis and play a role in mutagenesis induced by DNA damage. REV1 is deoxycytidyltransferase that incorporates dCMP opposite template abasic sites.In order to develop hypersensitive mouse model for radiation exposure, We have developed transgenic mouse (Tg) over expressing Rev1 gene under the constitutive zinc-induced transcriptional activation promoter. We've succeeded in establishing 7 Tg mouse line expressing Rev1 transgene. We examined sensitivity and mutation frequency of T-cell receptor (TCR) after radiation exposure, and found that Tg mouse was apt to have higher mutation frequency of TCR than normal mouse.2.Development of molecular bio-dosimery for low dose radiationIn order to develop molecular bio-dosimery, We have focused our research on functional analysis of Histone H2AX complex which is phosphorylated after induction of DNA damage (γ-H2AX) and visualized as foci in cell nucleus. We found that H2AX became highly mobile after induction of DSBs. We further find that mobilization depends not on phosphorylation but rather on ubiquitination, and that ubiquitination of H2AX is, in turn, regulated by TIP60 histone acetylase which implicates TIP60 in DNA repair. These results suggest that mobilization of H2AX is an early and necessary step in repair of DNA DSB.