© 1983 Oxford University Press
research-article |
The effects of dietary corn oil on the metabolism and activation of benzo[a]pyrene by the benzo[a]pyrene metabolizing enzymes of the mouse
Department of Pharmacology, School of Pharmacy, University of Georgia Athens, GA 30602, USA
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Male ICR Swiss mice, weighing 16 — 20 g, were fed ad libitum either a fat-free diet or a diet containing 10% com oil. After three weeks on these diets, the rates of benzo[a]pyrene (B[a]P) metabolite formation and metabolism to products which covalently bind with macromolecules were compared using hepatic nuclei and microsomal preparations. The maximum activity of B[a]P hydroxylase hi microsomes from untreated animals was increased 50% by feeding the com oil diet, however, B[a]P hydroxylase in microsomes from 3-methylcholanthrene (3-MC)-treated mice was unaffected by diet. In animals treated with phenobarbital, B[a]P metabolism and B[a]P - DNA adduct formation were greater hi microsomes from corn oil fed mice compared to those fed the fat-free diet. At a B[a]P concentration of 96 µM, microsomes from corn oil fed untreated mice produced 26% more extractable metabolites and covalent binding to exogenous DNA was increased 46%. At lower substrate concentrations (0.94–15.0 µM B[a]P), B[a]P-DNA and B[a]P -protein binding were 300 – 400% greater when incubated with microsomes from corn oil fed mice than when incubated with microsomes from mice fed fat-free diet. The apparent Vmax's determined for the formation of each extractable metabolite were increased 1.5 – 3.0 times by the corn oil diet. Hepatic nuclear B[a]P hydroxylase and nuclear activation of B[a]P to products which covalently bind to DNA in both non-induced and 3-MC-pretreated animals fed the corn oil diet were greater than that observed in animals fed the fat-free diet. B[a]P hydroxylase activities in the lungs of these animals were unaltered by diet.