Action of xanthine-xanthine oxidase system on microsomal benzo(a)pyrene metabolism in vitro.
The effect of superoxide anion-radical and other reactive oxygen species on the metabolism of benzo(a)pyrene was studied with isolated mouse liver microsomes. Reactive oxygen species were generated in vitro by xanthine-xanthine oxidase plus Fe3+ X FeEDTA and benzo(a)pyrene metabolism was followed by reverse-phase high pressure liquid chromatography. The following results were obtained: The reactive oxygen species induced one-electron oxidation of benzo(a)pyrene and increased production of free epoxide as well as protein-binding intermediates. The reactive oxygen species triggered microsomal lipid peroxidation in the presence of Fe3+ X FeEDTA. As a result of microsomal lipid peroxidation a decreased activity of cytochrome P-450, epoxide hydrolase and UDP-glucuronyltransferase was found. It is suggested that active oxygen species changed the balance between bioactivation and conjugation of benzo(a)pyrene metabolites causing accumulation of the epoxide and protein-binding intermediates. The role of iron ions and chelates in this process is discussed.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D010084:Oxidation-Reduction; D013481:Superoxides / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000494:pharmacology
D005965:Glucuronates; D008054:Lipid Peroxides; D013481:Superoxides; D001564:Benzo(a)pyrene; D009249:NADP; D004492:Edetic Acid; D014969:Xanthine Oxidase