Determination of genetic susceptibility factors for atmospheric toxic substances.

我们研究了柴油车尾气颗粒物有机提取物(OE-DEP)和城市细颗粒物(OE-UFP)对大鼠心脏微血管内皮细胞(RHMVE)的细胞毒性和氧化应激能力。暴露于OE-DEP和OE-UFP以及砷化合物后，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，空气中的砷是由煤燃烧产生的，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、丁硫氨酸亚磺胺和来自HO-1的siRNA对OE-DEP、OE-UFP和砷化合物对内皮细胞的细胞毒性的影响。N-乙酰半胱氨酸不影响谷胱甘肽水平，也不降低砷化合物的细胞毒性。丁硫氨酸亚磺胺降低细胞内谷胱甘肽水平，增强细胞毒作用和HO-1mRNA的表达。HO-1的siRNA转染降低了HO-1RNA水平，增强了砷化合物的细胞毒性，提示HO-1具有一定的抗氧化作用。同时对乙醛脱氢酶2基因进行SNP分析。

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.