DIETARY RESTRICTION MODULATED CARCINOGEN-DNA ADDUCT FORMATION AND THECARCINOGEN-INDUCED DNA STRAND BREAKS

Dietary restriction (DR) alters the activities of hepatic drug metabol izing enzymes and modulates the formation of carcinogen-DNA adducts in carcinogen treated animals. Our previous results showed that a 40% re striction of diet (60% of ad libitum (AL) food consumption) reduced th e hepatic metabolic activation of aflatoxin B-1 (AFB(1)) but increased the activation of benzo[a]-pyrene (BaP) in both rats and mice. In thi s study, the focus was directed toward the levels of carcinogen-DNA ad ducts formation and the carcinogen-induced DNA strand breaks in mouse kidney and liver DNA. DR significantly inhibited both AFB(1)-DNA adduc t formation and AFB(1)-induced DNA strand breaks in kidney DNA of mice that received a single dose of [H-3]AFB(1) (5 mg/kg). The levels of A FB(1)-DNA adduct formation in mouse kidney DNA correlated well with in creased AFB(1)-induced DNA strand breaks. The correlation between the levels of AFB(1)-DNA-adducts formed and DNA strand breaks in kidney DN A of DR-mice was less linear than between its AL-counterpart suggestin g that other factors, such as different rates of DNA repair, may be in volved. In addition, DR enhanced hepatic BaP- and 6-nitrochrysene (6-N C)-DNA adduct formation in the mice treated with BaP and 6-NC, respect ively. The formation of the specific BaP-adduct, anosinyl)-7,8,9-trihy droxy-7,8,9,10-tetrahydro-BaP (N-2-dG-BaP), in mouse liver was proport ional to the dose, and was compatible to the BaP-induced DNA strand br eaks affected by DR. The enhancement of the total 6-NC-DNA adduct form ation in DR-mouse was also in correlation with the increased 6-NC-indu ced DNA strand breaks. The activity of mouse liver microsomal nitro-re ductase increased by 2-fold in response to DR indicating that the nitr oreduction may contribute to the increase of the metabolic activation of 6-NC. Our present results indicate that the effect of DR on the car cinogen activation is dependent upon the DR-modulated carcinogen metab olizing enzyme activities. (C) 1997 Elsevier Science Ireland Ltd.