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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.
Drug Metab Dispos. 1994 May-Jun; 22(3):383-91.DM

Abstract

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)

Authors+Show Affiliations

Department of Food Science and Technology, Oregon State University, Corvallis 97331-6602.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8070314

Citation

Stresser, D M., et al. "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." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 22, no. 3, 1994, pp. 383-91.
Stresser DM, Bailey GS, Williams DE. 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. Drug Metab Dispos. 1994;22(3):383-91.
Stresser, D. M., Bailey, G. S., & Williams, D. E. (1994). 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. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 22(3), 383-91.
Stresser DM, Bailey GS, Williams DE. 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. Drug Metab Dispos. 1994 May-Jun;22(3):383-91. PubMed PMID: 8070314.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Stresser,D M, AU - Bailey,G S, AU - Williams,D E, PY - 1994/5/1/pubmed PY - 1994/5/1/medline PY - 1994/5/1/entrez SP - 383 EP - 91 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab Dispos VL - 22 IS - 3 N2 - 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) SN - 0090-9556 UR - https://www.unboundmedicine.com/medline/citation/8070314/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_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8070314 DB - PRIME DP - Unbound Medicine ER -