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1-Methylpyrene is a widespread pollutant that is carcinogenic in animals following metabolic activation.Previous studies have shown that benzylic hydroxylation of 1-methylpyrene, catalyzed by multiple CYP isoforms, gives rise to 1-hydroxymethylpyrene, which becomes bio-reactive following further metabolism by various sulfotransferase (SULT) isoforms.However, the mutagenic and chromosome damaging effects of 1-methylpyrene and 1-hydroxymethylpyrene in mammalian cells have not been investigated.In this study a Chinese hamster V79-derived cell line expressing both human CYP2E1 and human SULT1A1 was used to investigate the ability of 1-methylpyrene and 1-hydroxymethylpyrene to induce cytotoxicity (using the CCK-8 assay), micronuclei and Hprt gene mutations.The role of each enzyme was investigated through co-exposure in the presence of an enzyme inhibitor.We found that at concentrations of 0.5-4 μM and 5-20 μM, under conditions where no reduction in cell viability/growth occurred, 1-hydroxymethylpyrene and 1-methylpyrene induced micronuclei in V79-hCYP2El-hSULT1A1 cells in a concentration-dependent manner;however, both compounds were inactive in V79 cells.Similarly, they both caused an increase in Hprt mutant frequency in V79-hCYP2El-hSULT1A1 cells in these concentration ranges, with 1-methylpyrene impairing cell viability/growth at 10 μM and above in the mutagenicity assay.The compounds were again both inactive in V79 cells.The effects of 1-hydroxymethylpyrene in V79-hCYP2El-hSULT1A1 cells were blocked or reduced by addition of pentachlorophenol, a SULT1 inhibitor;the genotoxicity of 1-methylpyrene was significantly reduced by either 1-aminobenotrazole, a CYP2E1 inhibitor, or pentachlorophenol.The results suggest that human CYP2E1 and SULT1A1 cooperate to activate 1-methylpyrene and cause genotoxicity in mammalian cells.