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

我们尝试基于这些功能分析来开发超敏小鼠模型和使用DNA损伤反应蛋白的分子生物剂量学，以估计辐射暴露后的致癌风险和剂量。1．开发用于估计低剂量的超敏监测小鼠。辐射暴露及其生物学特性分析Y家族DNA聚合酶在维持遗传稳定性方面发挥着作用，Revl（Y家族DNA聚合酶的数量）具有脱氧胞苷基。转移酶活性并在称为易错 DNA 修复的跨损伤 DNA 合成中发挥核心作用为了开发对辐射暴露过敏的模型小鼠，我们培育了 Levi 转基因小鼠（Rev1 小鼠），因此 Levi 小鼠表现出对肿瘤发生的易感性增加。在致癌性损伤后，我们分析了该小鼠的生物学特性此外，为了确定增加的.RE … More V1如何影响细胞的生物学表型，用hREV1表达质粒转染人纤维肉瘤细胞。具有四环素调节系统，然后分离出稳定的亚系，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，修复后存活的细胞可能会增加突变的积累。 2.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，我们重点研究了包括组蛋白H2AX在内的基因组损伤位点的蛋白质复合物的功能分析。和 REV1 复合物，它们在细胞核中可视化并可计数。我们发现 H2AX 的 DNA 损伤依赖性修饰可增强染色质动力学。关于重构系统。

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

The first US-Japan meeting on error-prone DNA synthesis, Maui, Hawaii, December 20-21, 2004.

第一次美日关于易错 DNA 合成的会议，夏威夷毛伊岛，2004 年 12 月 20 日至 21 日。

• 发表时间: 2005
• 期刊: DNA Repair 4(6)
• 作者: Kamath-Loeb;AS.
• 通讯作者: AS.

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

緊急被ばく医療開発-次世代の分子バイオドシメトリー法の開発プロジェクト

紧急暴露医学发展-下一代分子生物剂量测定方法开发项目

• 发表时间: 2005
• 作者: Masuda;Y;神谷研二
• 通讯作者: 神谷研二

Network System for Radiation Emergency Medicine and the Role of Hiroshima University as the Center of Western Japan

辐射急救医学网络系统和广岛大学作为西日本中心的作用

• 发表时间: 2006
• 作者: Kamiya;K
• 通讯作者: K