Inhibition of aflatoxin B1-hepatocarcinogenesis in rats by beta-naphthoflavone

Effects of beta-naphthoflavone (beta NF) on the activity of hepatic microsomal aflatoxin B1 (AFB1)-4-hydroxylase - the cytochrome P-450-dependent enzyme system which catalyzes the metabolism of AFB1 to AFM1 - and on AFB1-induced in vivo hepatocarcinogenesis were investigated in weanling male Fischer rats. A single i.p. injection of beta NF in doses of 20 mg/kg and 150 mg/kg induced AFB1-4-hydroxylase 3- and 4-fold, respectively, 48 h post injection. Feeding of diet containing 0.01% beta NF for a period of 9-weeks induced AFB1-4-hydroxylase approximately 2-fold. AFB1, given by intubation in a dose of 25 micrograms five times/week for 8 weeks, produced 42 weeks later a 100% incidence of liver lesions (neoplastic foci, nodules or tumors), but feeding beta-NF in diet at a concentration of 0.015% for one week prior to and during the 8 weeks of AFB1 treatment inhibited AFB1 hepatocarcinogenesis by approximately 75%. These results are in accord with the suggestion that AFB1-4-hydroxylase induction may be associated with the inhibition of AFB1 carcinogenesis, possibly occurring as a consequence of accelerated detoxification of AFB1 via its conversion to AFM1.