Dietary lipotropes, hepatic microsomal mixed-function oxidase activities, and in vivo covalent binding of aflatoxin B1 in rats.
Weanling male Sprague-Dawley rats were fed either a nutritionally complete synthetic diet (Diet 1) or a diet marginally deficient in choline and methionine, and lacking folacin (lipotrope deficient, Diet 2) to determine the role of hepatic mixed-function oxidase metabolism of aflatoxin B1 (AFB1) in the Diet 2-induced enhancement of AFB1 hepatocarcinogenesis previously reported. Hepatic microsomal mixed-function oxidase activities, as assayed by ethylmorphine N-demethylation, ethoxycoumarin O-dealkylation, cytochrome c reduction, AFB1 metabolism, and cytochrome P-450 content, were all depressed by Diet 2. Furthermore, the proportion of an i.p. dose of AFB (1 mg/kg) that became covalently bonded to DNA and RNA was similarly reduced when measured 6 hr after administration. The formation of AFB1-protein adducts was not influenced by dietary treatment. The depression of DNA and RNA adduct formation in the Diet 2 animals was probably related to the lower mixed-function oxidase activities and not to an alteration of glutathione levels, which remained unchanged by dietary treatment. These results suggest that the marginally lipotrope-deficient diet does not enhance tumor formation through an increased microsomal activation of AFB1. Alternative hypotheses without data are suggested.
D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D004247:DNA / Q000378:metabolism; D008082:Lipotropic Agents / Q000008:administration & dosage*; D008114:Liver Neoplasms, Experimental / Q000209:etiology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats
D000348:Aflatoxins; D008082:Lipotropic Agents; D012313:RNA; D004247:DNA; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases