Indole-3-carbinol and beta-naphthoflavone induction of aflatoxin B1 metabolism and cytochromes P-450 associated with bioactivation and detoxication of aflatoxin B1 in the rat.

Aflatoxin B1 (AFB1) is a highly hepatotoxic and hepatocarcinogenic secondary metabolite of the grain mold Aspergillus flavus and related fungi. Indole-3-carbinol (I3C), found in cruciferous vegetables, can both inhibit and promote AFB1-induced carcinogenesis. We have examined the influence of dietary treatment with I3C and the well-known Ah receptor agonist beta-naphthoflavone (BNF) on the relative levels of different cytochrome P-450 (CYP) isoforms known to metabolize AFB1 in male Fischer 344 rats. After 7 days of feeding 0.2% I3C or 0.04% BNF, alone or in combination, the relative levels of hepatic CYP1A1, 1A2, 2B1/2, 2C11, and 3A were assessed by laser densitometry of Western blots. Both diets containing I3C markedly increased band densities of CYP1A1 (up to 24-fold), 1A2 (3.1-fold), and 3A1/2 (3.8-fold), and had lesser effects on the levels of 2B1/2 (1.8-fold) and no effect on CYP2C11. BNF also strongly increased band densities of CYP1A1 (12-fold) and 1A2 (2.7-fold), but had no effect on the levels of CYP2B1/2 or 3A1/2 band densities, and repressed those of CYP2C11 (2-fold). In addition, we examined the in vitro hepatic microsomal metabolism of AFB1 at 16, 124, and 512 microM substrate levels. Diets containing I3C elevated initial rates of AFM1 (a detoxication product) production 18.6- to 19.2-fold over control at 16 microM AFB1, which declined to 7.8- to 9.5-fold at 512 microM AFB1. The BNF-only diet gave similar, but less dramatic effects (5.9-fold at 16 microM AFB1, 3.5-fold at 512 microM AFB1).(ABSTRACT TRUNCATED AT 250 WORDS)