DECREASED LEVELS OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE-DNA ADDUCTS IN RATS TREATED WITH BETA-CAROTENE, ALPHA-TOCOPHEROL AND FREEZE-DRIED ALOE

To assess mechanisms of chemoprevention of hepatocarcinogenesis by tra ns-beta-carotene (beta-C), DL-alpha-tocopherol (alpha-T), and freeze-d ried whole leaves of Kidachi aloe (Aloe), formation of 2-amino-3-methy limidazo[4,5-f]quinoline (IQ)-DNA adducts was measured by P-32-post-la beling analysis, and CYP1A1 and CYP1A2 protein levels were analyzed by ELISA. Group 1 rats were fed diet containing 0.02% beta-C, 1.5% alpha -T Or 30% Aloe over an 8 day period, while group 2 was given basal die t alone. On day 7, all animals were subjected to two-thirds partial he patectomy (PH). Twelve hours after PH, they received a single dose of the carcinogenic food pyrolysate IQ (100 mg/kg) intragastrically, to i nitiate hepatocarcinogenesis. Rats were killed 6, 12, 24 and 48 h afte r IQ administration. The levels of adducts, expressed as relative addu ct labeling values in rats treated with beta-C, alpha-T and Aloe, were decreased as compared with the control group at hour 24 (36 h after P H), with a significant difference in the case of the beta-C group (46. 4% of the control value). Similarly, all showed a tendency for decreas e at hour 48. Furthermore, the levels of CYP1A2, known to be responsib le for activation of IQ, showed a significant reduction at hour 24. It is concluded that beta-C, and possibly also alpha-T and Aloe, have th e potential to reduce IQ-DNA adduct formation, presumably as a result of decreased formation of active metabolites. The results may explain, at least in part, the previously observed inhibitory effects of these compounds on induction of preneoplastic hepatocellular lesions.