Dietary Lipotropes, Hepatic Microsomal Mixed-Function Oxidase Activities, and in VivoCovalent Bindingof Aflatoxin B1in Rats1

Weanling male Sprague-Dawbeyrats were fed either a nutritionallycomplete synthetic diet (Diet 1) or a diet marginallydeficient in cholineand methionine,and lack ing folacin (lipotropedeficient, Diet 2) to determine the role of hepatic mixed-functionoxidase metabolism of aflatoxinB, (AFB1)in the Diet 2-inducedenhancementof AFB hepatocarcinogenesispreviouslyreported. Hepatic microsomalmixed-functionoxidaseactivities,as assayed by ethylmorphine N-demethylation, ethoxycoumarin alkylation, cytochrome C reduction, AFB metabolism, and cytochrome P-450 content, were all depressed by Diet 2. Furthermore,the proportionof an i.p. doseof AFB (1 mg/ kg) that becamecovalentlybondedto DNA and RNAwas similarly reduced when measured6 hr after administra tion. The formationof AFB1-proteinadductswas not influ enced by dietary treatment. The depressionof DNA and RNAadductformationin the Diet 2 animalswas probably rebatedto the lowermixed-functionoxidaseactivitiesand not to an alterationof glutathionelevels,whichremained unchangedby dietary treatment. These results suggest that the marginallybipotrope-deficient diet does not en hancetumorformationthroughan increasedmicrosomal activationof AFB,. Alternative hypotheseswithout data