Clarification of factors governing sensitivity of disruption of intracellular receptor-xenobiotic metabolizing enzyme signaling pathways by chemical substances

本研究的成果概括如下：1）为筛选有毒环境污染物，我们成功地开发了表达野生动物细胞内受体蛋白的体外检测系统，2）细胞内受体蛋白对暴露于有毒环境污染物表现出种特异性和亚型特异性反应，3）体外测定系统使我们能够评估在一些野生种群中引入物种间易感性差异的风险，4）进化突变的某些氨基酸残基有助于细胞内受体和细胞色素P450的配体相互作用，（5）除细胞内受体和细胞色素P450外，还有其他因素对易感性起作用。

The achievements of this study are summarized as follows;1) for the screening of toxic environmental pollutants, we succeeded in developing in vitro assay systems that intracellular receptor proteins of wild animals are expressed, 2) the intracellular receptor proteins showed species- and isoform-specific responses to the exposure to toxic environmental pollutants, 3) the in vitro assay systems enabled us to assess the risk incorporating the interspecies differences in susceptibility in some wild populations, 4) certain amino acid residues that were evolutionary mutated contribute to the ligand interaction of intracellular receptors and cytochrome P450, and 5) there are factors responsible for the susceptibility other than intracellular receptors and cytochrome P450.