Effects of unsaturated fatty acids on metabolism of benzo[a]pyrene in an NADPH-fortified rat liver microsomal system.
Modulation of microsome mediated benzo[a]pyrene (BP) metabolism by oleic and linoleic acids was studied. Oleic and linoleic acids did not influence the apparent activity of aryl hydrocarbon hydroxylase or the relative ratios of BP-7,8-dihydrodiol to phenol metabolites on high performance liquid chromatography. The total binding of BP-metabolites to DNA was not influenced much by the presence of oleic acid, but was inhibited significantly by linoleic acid (p less than 0.05). The quantity of BP-metabolite bound adducts was determined by Sephadex LH-20 column chromatography with a methanol gradient. The amount of adducts bound with the anti-isomer of BP-7,8-dihydrodiol-9,10-oxide (diol-epoxide) was more than that with 9-hydroxybenzo[a]pyrene-4,5-oxide in the absence of fatty acids, and vice versa in the presence of fatty acids. The presence of 1, 2 or 5 microliters/ml oleic acid decreased the amounts of adducts with the anti- and syn-isomers of the diol-epoxide but not those with 9-hydroxybenzo[a]pyrene-4,5-oxides, whereas the presence of 0.08 - 2 microliters/ml of linoleic acid decreased the amounts of all these adducts but to different extents, resulting in predominance of 9-hydroxybenzo[a]pyrene-4,5-oxide derived adducts over anti-isomer adducts of the diol-epoxide. These observations suggest that endogenous materials that do not have any enzyme activity may have important influences on the metabolism of chemical carcinogens.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D004247:DNA / Q000378:metabolism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D051381:Rats
D001580:Benzopyrenes; D008041:Linoleic Acids; D009829:Oleic Acids; D019301:Oleic Acid; D001564:Benzo(a)pyrene; D009249:NADP; D004247:DNA; D019787:Linoleic Acid; D001189:Aryl Hydrocarbon Hydroxylases