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

开发用于低剂量辐射评估和致癌风险评估的生物剂量测定法

• 批准号: 17310036
• 负责人: KAMIYA Kenji
• 金额: $ 10.86万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17310036/
• 关键词: 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

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

本研究尝试建立小鼠过敏模型，并利用DNA损伤反应蛋白进行分子生物剂量学研究，以评估辐射后致癌风险和剂量.低剂量辐射敏感性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重要作用。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，具有脱氧胞苷酰转移酶活性，在跨损伤DNA合成中起核心作用，称为易错DNA修复。为了建立辐射致敏小鼠模型，我们建立了Levi转基因小鼠（Rev1小鼠）。因此，Levi小鼠在受到致癌物损伤后，表现出对肿瘤发生的易感性增加，我们对该小鼠的生物学特性进行了分析。此外，为了确定如何增加.RE ...更多信息 V1影响细胞的生物学表型，将具有四环素调控系统的hREV 1表达质粒转染人纤维肉瘤细胞，获得稳定的细胞亚系。我们发现，表达hREV 1的细胞对X射线照射的细胞毒性作用的抵抗力比亲本细胞更强。这一观察结果表明，在受损DNA的修复过程后，存活的细胞可能会增加突变的积累。低剂量辐射分子生物剂量学的发展研究为了发展新的分子生物剂量学，我们重点研究了基因组损伤位点蛋白复合物的功能分析，包括细胞核中可见的、可计数的组蛋白H2AX和REV 1复合物。我们已经发现了可能的候选分子的分子生物剂量学。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系统上的跨损伤DNA合成。少

项目成果

Dynamics of human replication factors in the elongation phase of DNA replication.

• DOI: 10.1093/nar/gkm822
• 发表时间: 2007
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Masuda Y;Suzuki M;Piao J;Gu Y;Tsurimoto T;Kamiya K
• 通讯作者: Kamiya K

損傷乗り越えDNA合成と発癌

克服损伤和致癌作用的 DNA 合成

• 发表时间: 2007
• 期刊: ゲノム医学 7・1
• 作者: Watanabe;H.;増田雄司
• 通讯作者: 増田雄司

Translesion DNA synthesis and cancer

跨损伤 DNA 合成与癌症

• 发表时间: 2007
• 期刊: Genome Medicine 7(1)
• 作者: Masuda;Y
• 通讯作者: Y

Mechanism of radiation carcinogenesis

放射性致癌机制

• 发表时间: 2006
• 期刊: The Journal of The Hiroshima Medical Association 59(4)
• 作者: Kamiya;K
• 通讯作者: K

小腸線窩再生と生存率を用いたマウスにおける発酵乳の放射線防御作用

发酵乳对小鼠小肠窝再生的辐射防护作用和存活率

• 发表时间: 2006
• 期刊: 広島医学 59・4
• 作者: Masuda;Y.;明神有紀
• 通讯作者: 明神有紀