Determination of genetic susceptibility factors for atmospheric toxic substances.

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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.