© 1983 Oxford University Press
research-article |
Effects of unsaturated fatty acids on metabolism of benzo[a]pyrene in an NADPH-fortified rat liver microsomal system
Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan
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-di-hydrodiol 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 <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 µl/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 µl/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.