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)
Stresser
D M
DM
Department of Food Science and Technology, Oregon State University, Corvallis 97331-6602.
Bailey
G S
GS
Williams
D E
DE
D016604:Aflatoxin B1 / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics*; D016607:Aflatoxin M1 / Q000378:metabolism; D000348:Aflatoxins / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology*; D001711:Biotransformation; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction; D008658:Inactivation, Metabolic; D007211:Indoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344; D019324:beta-Naphthoflavone
D000348:Aflatoxins; D016588:Anticarcinogenic Agents; D001571:Benzoflavones; D007211:Indoles; D007527:Isoenzymes; C006426:aflatoxin B1-2,3-oxide; C033759:aflatoxin Q1; D019324:beta-Naphthoflavone; D016607:Aflatoxin M1; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; C016517:indole-3-carbinol