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

我们尝试在这些功能分析的基础上建立过敏小鼠模型和利用DNA损伤反应蛋白的分子生物剂量学来估计辐射暴露后的致癌风险和剂量。低剂量辐射暴露超敏监测小鼠的研制及其生物学特性分析y家族DNA聚合酶在维持遗传稳定性中起作用。聚合酶的功能障碍影响癌症易感性。Revl是y家族DNA聚合酶的编号，具有脱氧胞基转移酶活性，在易出错DNA修复的翻译DNA合成中起核心作用。为了建立辐射暴露过敏模型小鼠，我们培育了Levi转基因小鼠（Rev1小鼠）。因此，Levi小鼠在癌变损伤后对肿瘤的易感性增加，我们分析了该小鼠的生物学特性。此外，确定如何增加。利用具有四环素调控系统的hREV1表达质粒转染人纤维肉瘤细胞，分离出稳定的亚型。我们发现表达hREV1的细胞比亲本细胞更能抵抗x射线照射的细胞毒性作用。这一观察结果表明，存活的细胞可能在受损dna修复过程后增加了突变的积累。低剂量辐射分子生物剂量学的发展研究为了开发新的分子生物剂量学，我们重点研究了基因组损伤部位的蛋白复合物的功能分析，包括Histone H2AX和REV1复合物，这些蛋白复合物在细胞核中可见为病灶和可计数。我们已经检测到可能用于分子生物计量学的候选分子。我们发现H2AX的DNA损伤依赖性修饰增强了染色质动力学。我们还成功地分析了在重组体系上的翻译DNA合成。少

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