Inhibition of aflatoxin B1 mutagenicity by cyclopiazonic acid in the presence of human liver preparations.
Co-occurrence of cyclopiazonic acid (CPA) and aflatoxin B(1) (AFB(1)) has been reported in different food commodities. Recently, we have shown that CPA reduces AFB(1) mutagenicity in the standard Salmonella-Microsome-Assay using rat S9-mix for metabolic activation (Environ. Toxicol. Pharmacol. 11 (2002) 207). When using S9-mix prepared from individual liver fractions of human patients, CPA was found to be non-mutagenic, but exerted a significant reduction of the mutagenicity of AFB(1). Moreover, CPA was shown to inhibit testosterone hydroxylation, but not methoxyresorufin dealkylation (MROD), in human S9. Thus, the reduction of the AFB(1) mutagenicity by CPA may be attributed to the inhibitory effect of CPA on cytochrome P450 (CYP450) 3A4 activity. These findings might be of relevance to the epidemiology of food-borne mycotoxicosis as similar molar ratios to those investigated here have been reported in food commodities.
Sabater Vilar
Monica
M
Department of Veterinary, Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 16, P.O. Box 80.152, 3508 TD Utrecht, Netherlands. m.sabater@vfft.vet.uu.nl
Kuilman-Wahls
Mariella E M
ME
Fink-Gremmels
Johanna
J
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors* / Q000633:toxicity; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008110:Liver Extracts; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D014020:Tissue Extracts / Q000494:pharmacology
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles; D008110:Liver Extracts; D009153:Mutagens; D014020:Tissue Extracts; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019388:Cytochrome P-450 CYP1A2; C000543:cyclopiazonic acid