Effect of Caloric Restriction on the Metabolism of Benzo[a]pyrene (BaP) and the Formation of BaP-DNA Adducts in Male Fischer 344 Rats

Abstract

The effect of caloric restriction (CR) on activities of xenobiotic metabolizing enzymes results in alterations in the metabolic activation of chemical carcinogens, with a resultant impact on DNA-carcinogen adduct formation. Using benzo[a]pyrene (BaP) as a model carcinogen, we have studied the effect of CR on the metabolic activation of BaP, in terms of both BaP metabolism and BaP-DNA adduct formation. Male Fischer 344 rats fed CR diets (60% of the food consumption of ad libitum−fed rats) showed higher activities of BaP metabolizing enzymes resulting in increases of BaP metabolism in vitro and BaP-DNA adduct formation in vivo. The results of the study of the effect of CR on the in vitro metabolism of BaP showed that CR increased the total BaP metabolism, as well as BaP-t-9, 10-diol and BaP-t-4, 5-diol formation. However, BaP-t-7, 8-diol, a proximate carcinogenic metabolite of BaP, was decreased by liver microsomes from CR-rats. Our results indicate that the effect of CR on metabolic activation of a chemical carcinogen was dependent upon the selected xenobiotic metabolizing enzymes whose activity may be significantly altered by CR.

Key Words:

• Caloric restriction
• benzo[a]pyrene (BaP)
• rat liver microsomes
• DNA binding
• BaP-DNA adduct
• BaP metabolism