Screening of Biodefense Factors for Toxicity of Environmental Pollutants or Irradiation

环境污染物或辐射毒性生物防御因子的筛选

基本信息

批准号：
07558201
负责人：
NAGANUMA Akira
金额：
$ 2.43万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07558201/
关键词：
Environmental Pollutants Screening Biodefense Factor Yeast Resistance Methylmercury Irradiation 防御遺伝子

项目摘要

Some biodefense factors, such as antioxidation enzymes or glutathione, against toxicity of environmental pollutants in cells have been known. However, there is the possibility that other factors more important than these known factors are exist in the cells and tissues. Determination of unknown biodefense factors may be essential to evaluate toxicity of the environmental pollutants.We tried to identify the genes for biodefense factors against toxicity of methylmercury which was selected as a typical environmental pollutant. Yeast clone exhibited resistance to methylmercury was obtained by transfection of plasmid carrying genomic library of yeast. Segregation of the introduced plasmid eliminated methylmercury resistance of the clone, and retransfection of the plasmid isolated from the clone gave methylmercury resistance to the parent yeast. The gene responsible for the methymercury resistance was isolated from the plasmid, and the sequence was examined. Because the protein homologous to the product of this gene has been observed not only in yeast but also in human and other mammals, the gene product may be involved in methylmercury resistance in various species. The gene encodes an enzyme whose activity is inhibited by methylmercury. There is the possibility that the enzyme is a target molecule for methylmercury toxicity.On the other hand, we also studied the mechanism of protective effect of radiodefense drug, bismuth nitrate, against toxic effect of gamma-irradiation. We found that bismuth compounds induce the synthesis of metallothionein in the bone marrow and metallothionein has a role as biodefense factor for toxic effect of gamma-irradiation. We also found that metallothionein regulates expression of other genes in mammalian cells. There is the possibility that protective effect of metallothionein against gamma-irradiation is due to expression of the gene which encodes a defense factor.

已知一些生物防御因子，例如抗氧化酶或谷胱甘肽，可以抵抗细胞中环境污染物的毒性。然而，细胞和组织中可能存在比这些已知因素更重要的其他因素。未知生物防御因子的测定对于评估环境污染物的毒性可能至关重要。我们尝试鉴定针对典型环境污染物甲基汞毒性的生物防御因子的基因。通过转染携带酵母基因组文库的质粒获得表现出甲基汞抗性的酵母克隆。引入的质粒的分离消除了克隆的甲基汞抗性，并且从克隆中分离的质粒的再转染赋予了亲本酵母的甲基汞抗性。从质粒中分离出负责甲基汞抗性的基因，并检查了序列。由于与该基因产物同源的蛋白质不仅在酵母中而且在人类和其他哺乳动物中也被观察到，因此该基因产物可能与多种物种的甲基汞抗性有关。该基因编码一种酶，其活性被甲基汞抑制。该酶有可能是甲基汞毒性的靶分子。另一方面，我们还研究了放射防御药物硝酸铋对γ射线毒性作用的保护作用机制。我们发现铋化合物诱导骨髓中金属硫蛋白的合成，并且金属硫蛋白具有作为伽马射线辐射毒性作用的生物防御因子的作用。我们还发现金属硫蛋白调节哺乳动物细胞中其他基因的表达。金属硫蛋白对伽马射线的保护作用可能是由于编码防御因子的基因的表达所致。