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

我们试图基于这些功能分析来开发使用DNA损伤反应蛋白的高敏小鼠模型和分子生物学中的分子，以估计辐射暴露后的致癌风险和剂量。1。高剂量辐射暴露的高度监测小鼠的发展及其生物学特征的分析Y-家庭DNA聚合酶在维持遗传稳定性方面起着作用。聚合酶的故障会影响癌症的敏感性。 Revl是Y-家族DNA聚合酶的数量，具有脱氧胞屈转移活性，并在被称为易易折叠DNA修复的Translesion DNA合成中起着核心作用。为了开发高敏模型以进行辐射暴露，我们已经生成了Levi转基因小鼠（Rev1小鼠）。因此，Levi小鼠在致癌性损伤后显示出对肿瘤发生的敏感性增加，我们分析了该小鼠的生物学特征。此外，为了确定增加……更多的V1影响细胞的生物学表型，用具有四环素调节系统的HREV1表达质粒翻译了人纤维肉瘤细胞，然后分离了稳定的subline。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。该观察结果表明，幸存的细胞可能会增加受损DNA的修复过程后突变的积累。2。研究低剂量辐射蛋白的分子生物分类的开发，以开发新的分子生物脱偶联，我们将研究集中在基因组受损部位的蛋白质复合物的功能分析上，包括组蛋白H2AX和REV1复合物，这些蛋白质复合物在细胞核中可视化为焦点和可见的foci和可见。我们已经检测到分子生物界面的可能候选分子。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对重构系统的跨性别DNA学术。较少的

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