EFFECT OF CALORIC RESTRICTION ON THE METABOLIC-ACTIVATION OF XENOBIOTICS

The effect of caloric restriction (CR) on xenobiotic metabolizing enzyme activities results in alterations in the metabolic activation of chemical carcinogens, with a resultant impact on DNA-carcinogen adduct formation and DNA repair. Using aflatoxin B1 (AFB1) and benzo[a]pyrene (BP) as model carcinogens, we studied the effect of CR on the metabolic activation of these carcinogens and carcinogen-induced DNA damage and repair in terms of AFB1-DNA and BP-DNA adduct formation and removal. Male Fischer 344 rats fed calorie restricted diets (60% of the food consumption for ad libitum-fed rats) showed a reduction in the metabolic activation of AFB1 and decrease in both the in vitro and in vivo AFB1-DNA adduct formation. However, CR increased the activity of BP metabolizing enzymes resulting in an enhancement of BP-DNA adduct formation. Our results indicate that the effect of CR on metabolic activation of xenobiotics is dependent upon the selected xenobiotic metabolizing enzymes whose activities may be significantly altered by CR, and upon the nature of the chemical carcinogens which exert different structure-activity relationships during the process of chemically induced carcinogenesis.