Cytochrome P450 enzymes involved in the metabolism of aflatoxin B1 in chickens and quail.
A study was conducted to identify the cytochrome P450 (CYP, CYP450) enzyme orthologs involved in the bioactivation of aflatoxin B(1) (AFB(1)) into the highly toxic metabolite known as aflatoxin-8,9-epoxide (AFBO) in quail and chicken hepatic microsomes. The strategies used included the use of specific CYP450 inhibitors and the correlation of prototype substrate activities with AFBO production. Additionally, the presence of the enzymes was qualitatively determined using an immunoblotting technique. The results showed that both quail and chicken microsomes have CYP1A1, CYP1A2, CYP2A6, and CYP3A4 enzymatic activity. A strong relationship between CYP1A1 and CYP2A6 activities and AFB(1) bioactivation was found in both species. Inhibition studies provided more evidence for the role of CYP2A6 in the bioactivation of AFB(1). The immunoblot results showed clear bands for the CYP2A6 and CYP3A4 orthologs in both species. The results of the present study indicate that CYP2A6 and, to a lesser extent, CYP1A1 are responsible for the bioactivation of AFB(1) into AFBO in both quail and chicken hepatic microsomes.
Diaz
G J
GJ
Laboratorio de Toxicología, Facultad de Medicina Veterinaria y de Zootecnia, Universidad Nacional de Colombia, Bogotá, D.C. Colombia. gjdiazg@unal.edu.co
Murcia
H W
HW
Cepeda
S M
SM
D016604:Aflatoxin B1 / Q000378:metabolism*; D000818:Animals; D002645:Chickens / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology*; D011784:Quail / Q000378:metabolism*
D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A