Stimulation of binding of benzo[a]pyrene metabolites to DNA by diet-induced peroxidative stress.
To investigate the influence of unsaturation of dietary fat on the oxidation of benzo[a]pyrene-7,8-dihydrodiol to DNA binding products, we fed diets containing 10% by weight of either safflower oil or lard to weanling rats. Compared with the group fed lard, the group fed safflower oil had 2.0- to 2.5-fold higher levels of unstimulated and peroxidation-stimulated activation of benzo[a]pyrene-7,8-dihydrodiol to DNA-binding metabolites, respectively, in hepatic nuclei. The rats fed safflower oil had a significant 75% higher level of lipid peroxidation as measured by the thiobarbituric acid assay. Rats fed safflower oil also showed 30% greater binding of (-)-benzo[a]pyrene-7,8-dihydrodiol oxidation products to DNA compared with animals fed lard, following administration of this dihydrodiol enantiomer through the hepatic portal vein. Significant diet-dependent differences were not apparent in DNA binding of the (+)-isomer, or in the tetrol production from either isomer; however, rats fed safflower oil showed a trend towards production of higher levels of anti-benzo[a]pyrene diol epoxide-derived tetrols. Activities of hepatic nuclear and microsomal aryl hydrocarbon hydroxylase and of cytosolic and microsomal glutathione S-transferases were not significantly affected by diet, nor was the activity of microsome-mediated binding of (+)- or (-)-benzo[a]pyrene-7,8-dihydrodiol to DNA in vitro. The results indicate that polyunsaturated fat in quantities as low as 10% by weight of the diet is sufficient to increase significantly the extent to which DNA-binding metabolites of benzo[a]pyrene are produced, and that this increased metabolism is likely to be independent of mixed-function oxidases.
Kwei
G Y
GY
Department of Nutritional Sciences, University of California, Berkeley 94720.
Bjeldanes
L F
LF
D000818:Animals; D004247:DNA / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012450:Safflower Oil / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D004101:Dihydroxydihydrobenzopyrenes; C017228:benzo(a)pyrene 7,8-dihydrodiol; D012450:Safflower Oil; D004247:DNA; C029310:lard