Inhibition of microsome-mediated benzo[a]pyrene metabolism by hemin.
The effects of hemin on the metabolism of benzo[a]pyrene (BP) in rat liver microsomes were studied. Hemin inhibited the activity of aryl hydrocarbon hydroxylase and the metabolic activation of BP to forms able to bind to DNA. Analyses by high performance liquid chromatography of metabolites of BP revealed that hemin reduced their production and changed their relative amounts. The decrease in the amount of BP-7,8-dihydrodiol was greater than that in the amount of phenols. The elution profile of BP-metabolite-bound deoxyribonucleosides on Sephadex LH-20 column chromatography indicated that the formation of adducts with BP-7,8-dihydrodiol-9,10-oxide was decreased by hemin more than the formation of those with phenol derivatives. The present results suggest that endogenous components that are not enzymes are important modifiers of the biological activities of chemical carcinogens.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D001564:Benzo(a)pyrene; D006418:Heme; D006427:Hemin; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases