EFFECTS OF DIETARY RESTRICTION AND FASTING ON SELECTED RAT-LIVER ENZYMES OF XENOBIOTIC METABOLISM AND ON AOM-INDUCED DNA GUANINE METHYLATION IN RAT-LIVER AND COLON

Using five- to eight-week-old male F344 rats and a high-fat (23.5% cor n oil) modified AIN-76A diet, we examined the effects of dietary restr iction (a 3-wk 30% reduction of food intake with respect to ad libitum -fed controls) or complete fasting (2 days without food) on the activi ties of hepatic xenobiotic metabolizing enzymes in vitro and on azoxym ethane- (AOM) induced formation of O-6-methylguanine and 7-methylguani ne in liver and colon DNA in vivo. Compared with ad libitum-fed rats, fasting increased total liver cytochrome P450 by 32%, microsomal anili ne hydroxylase by 270%, N-nitrosodimethylamine demethylase by 270%, an d azoxymethane hydroxylase by 320%. Liver benzo[a]pyrene (BP) hydroxyl ase and glutathione-S-transferase were decreased by 39% and 21%, respe ctively, whereas NADPH cytochrome c reductase and UDP glucuronyltransf erase were unchanged. DNA methylation in the livers of fasted animals was 20-31% greater six hours after a 15 mg/kg sc injection of AOM than in ad libitum-fed controls, whereas DNA methylation in the colon was slightly lower. In three-week diet-restricted animals, there were smal l but not statistically significant changes in the various enzyme acti vities and in AOM-induced DNA methylation compared with the ad libitum -fed controls, with the exception of BP hydroxylase, which showed a 26 % decrease. However, the trends in the increase or decrease of each pa rameter, although small in magnitude, were similar to those observed i n the case of fasting, suggesting that the effects might become signif icant if the duration of diet restriction were prolonged. The enhancem ent of AOM metabolism in rat liver by fasting, leading to increased li ver DNA methylation, is different from that produced by chemical induc ers, such as ethanol, where no increase in liver DNA methylation is ob served.