title: Bioactivation of aflatoxin B1 by turkey liver microsomes: responsible cytochrome P450 enzymes.
abstract: 1. A study was conducted to determine the cytochrome P450 enzymes responsible for the bioactivation of aflatoxin B1 into its epoxide form (AFBO) in turkey liver microsomes. 2. The strategies used included the measurement of prototype substrate activity for specific human P450s, use of selective inhibitors, determination of correlation between aflatoxin bioactivation and enzymatic activity of prototype substrates and the determination of immunoreactive proteins using antibodies against human P450s. 3. Enzymatic activity and immunoreactive proteins corresponding to the turkey orthologs CYP1A1, CYP1A2, CYP2A6 and CYP3A4 were detected, but not for the CYP2D6 ortholog. 4. The results of the inhibition and correlation studies strongly suggest that the turkey CYP2A6 ortholog and, to a lesser extent, the CYP1A1 ortholog, are involved in the bioactivation of aflatoxin B1 in turkey liver microsomes. 5. This is the first study reporting the role of CYP2A6 in the bioactivation of AFB1 in an avian species and the role of CYP1A1 in any species.
authors.affiliation: Laboratorio de Toxicologia, Facultad de Medicina Veterinaria y de Zootecnia, Universidad Nacional de Colombia, Bogota, D.C. Colombia. gjdiazg@unal.edu.co
authors.forename: G J
authors.initials: GJ
authors.lastname: Diaz
authors.forename: H W
authors.initials: HW
authors.lastname: Murcia
authors.forename: S M
authors.initials: SM
authors.lastname: Cepeda
mesh_terms: D016604:Aflatoxin B1 / Q000378:metabolism*; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015151:Immunoblotting; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008730:Methoxsalen / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D014422:Turkeys / Q000378:metabolism*
chemical_list: D001571:Benzoflavones; D004791:Enzyme Inhibitors; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D008730:Methoxsalen