Determination of genetic susceptibility factors for atmospheric toxic substances.

我们已经解决了柴油机尾气颗粒物（OE-DEP）和城市细颗粒物（OE-UFP）的有机提取物在大鼠心脏微血管内皮细胞（RHMVE）的细胞毒性和氧化应激效力。暴露于OE-DEP和OE-UFP以及砷剂后，包括血红素加氧酶-1（HO-1）在内的抗氧化酶的mRNA水平增加。据报道，空气中的砷来自燃煤，在发展中国家造成慢性砷中毒。我们研究了N-乙酰半胱氨酸、丁硫氨酸亚砜亚胺和针对HO-1的siRNA对OE-DEP、OE-UFP和砷剂在内皮细胞中的细胞毒性的影响。N-乙酰半胱氨酸不影响谷胱甘肽水平，并降低砷剂的细胞毒性。丁硫克百威亚砜亚胺降低细胞谷胱甘肽水平，增强细胞毒性和HO-1 mRNA表达。转染HO-1的siRNA可降低HO-1的RNA水平，增强除二烷基酚类化合物外的砷类化合物的细胞毒性，表明HO-1在抗氧化作用中起作用。SNP分析也被用来研究乙醛脱氢酶2的多态性。

We have addressed cytotoxicity and oxidative-stress potency of organic extracts of diesel exhaust particles (OE-DEP) and urban fine particles (OE-UFP) in rat heart microvessel endothelial (RHMVE) cells. mRNA levels of antioxidant enzymes including heme oxygenase-1 (HO-1) were increased following exposure to OE-DEP and OE-UFP as well as arsenicals. It has been reported that airborne arsenicals generate from coal combustion and cause chronic arsenicism in developing countries. We investigated effects of N-acetylcysteine, buthionine sulfoximine, and siRNA fro HO-1 on cytotoxicity of OE-DEP, OE-UFP, and arsenicals in endothelial cells. N-acetylcysteine did not affect the glutathione levels and reduce the cytotoxicity of arsenicals. Buthionine sulfoximine decreased cellular glutathione level and enhanced the cytotoxicity and expression of HO-1 mRNA. Transfection with siRNA for HO-1 decreased the HO-1 RNA level and enhanced the cytotoxicity of arsenicals except for dialkylarsenicals, suggesting that HO-1 plays a role in antioxidant effects. SNP analyzes were also performed to investigate polymorphism of acetaldehyde dehydrogenase 2.