The effect of dietary imbalances on the activation of benzo[a]pyrene by the metabolizing enzymes from rat liver.
Male Sprague-Dawley rats (70-80 g) were fed ad libitum a standard control diet (22% casein, 5% lard), or a high lipid diet (30% lard) or a low protein diet (6% casein) or a standard diet containing 50 ppm phenoclor DP6. After 6 weeks on these diets, the cytochrome P-450 microsomal content, the benzo[a]pyrene monooxygenase (BaP-MO) and the epoxide hydrolase (EH) were assayed. The formation of mutagenic B(a)P metabolites which covalently bind with DNA was compared. The activity of BaP-MO and of EH were increased by the high lipid diet (+27% and 106% respectively) and by the phenoclor DP6 treatment (+63% and 400% respectively), compared to the standard diet. In animals fed a low protein diet the BaP-MO was decreased (-34%) and the EH activity was strongly increased (+262%) compared to those fed a standard diet. All experimental diets increased both the activation of BaP to metabolites able to bind DNA and the mutagenicity of BaP versus TA98 Salmonella typhimurium strain. It was concluded that dietary imbalances can be considered as a factor in chemical carcinogenesis.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism*; D001711:Biotransformation / Q000187:drug effects; D003043:Cocarcinogenesis; D004249:DNA Damage; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009152:Mutagenicity Tests; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D004041:Dietary Fats; D004044:Dietary Proteins; D001564:Benzo(a)pyrene; C013191:phenoclor; D011078:Polychlorinated Biphenyls; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D004851:Epoxide Hydrolases