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.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004032:Diet; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D008658:Inactivation, Metabolic; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014675:Vegetables; D019324:beta-Naphthoflavone
D000348:Aflatoxins; D001571:Benzoflavones; D005419:Flavonoids; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1