IN-VITRO CYTOCHROME-P450 MONOOXYGENASE AND PROSTAGLANDIN H-SYNTHASE MEDIATED AFLATOXIN-B(1) BIOTRANSFORMATION IN GUINEA-PIG TISSUES - EFFECTS OF BETA-NAPHTHOFLAVONE TREATMENT

In the present study, we examined the effects of treating guinea pigs with beta-naphthoflavone (BNF) on aflatoxin B1 (AFB1) metabolism by mi crosomal cytochrome P450 monooxygenase (P450) and prostaglandin H synt hase (PHS) in liver, lung and kidney tissues. After BNF treatment, mic rosomal 7-ethoxyresorufin 0-deethylase activity was induced 13-, 25- a nd 11-fold in lung, kidney and liver, respectively, confirming that th e BNF treatment protocol was effective at inducing monooxygenase activ ity. Treatment of guinea pigs with BNF did not change [H-3]AFB1-DNA bi nding catalyzed by microsomal PHS or P450 in lung, kidney or liver. In contrast, AFM1 formation by P450 was significantly increased in micro somes from all three organs. The data indicate that BNF-inducible P450 isozymes of the P4501A class are responsible for the biotransformatio n of AFB1 to non-toxic metabolites. Guinea pig kidney microsomes could also catalyze NADPH-dependent formation of aflatoxicol (AFL), a metab olite usually produced by a cytosolic steroid dehydrogenase. Renal mic rosomal AFL formation was not altered by prior BNF treatment. The resu lts in the present study suggest that BNF may alter the bioactivation of AFB1 in guinea pig tissues by inducing P450 activity, leading to th e formation of less reactive metabolite.