New evaluation system of cell damage caused by environmental chemicals that effect lifestyle diseases

1.柴油机尾气颗粒物中菲醌的细胞毒性菲醌对体外培养的人肺A549细胞有较强的毒性作用。2.砷化合物的细胞毒性砷激活转录因子Nrf 2并激活HO-1、Prx I和A170等基因的表达，蛋白质以泛素结合形式积累。萝卜硫素是一种激活Nrf 2的天然化合物，对砷中毒具有保护作用。3.生活方式相关疾病模型小鼠的分析突变小鼠对Fe-NTA的组织氧化损伤表现出更高的敏感性。小鼠清除硝酰基自由基的能力较低。我们还构建了A170缺陷型小鼠。这些老鼠表现出暴饮暴食和肥胖，导致胰岛素抵抗。

1.Cytotoxicity of phenanthraquinone contained in diesel exhaust particlesPhenanthraquinone showed strong toxicity to cultured human A549 cells derived from lung. Phenanthroline protected cells from toxicity of phenanthraquinone.2.Cytotoxicity of arsenic compoundsArsenic activates transcription factor Nrf2 and activate expression of genes such as HO-1,Prx I and A170, the protein accumulated as ubiquitin-conjugated form. Sulforaphane, Nrf2 activating natural compounds, had a beneficial effects against arsenic toxicity.3.Analysis of model mice in lifestyle-related illnessesWe constructed Prx I-deficient transgenic mice. The mutant mice showed higher sensitivity of tissue oxidative damage to Fe-NTA. The mice showed lower capacity to remove nitroxyl radicals. We also constructed A170-deficient mice. These mice show overeating and obesity, causing insulin-resistance.