Purified form of cytochrome P-450 from rainbow trout with high activity toward conversion of aflatoxin B1 to aflatoxin B1-2,3-epoxide.
Aflatoxin B1, the most potent hepatic chemical carcinogen known, is activated to the putative product aflatoxin B1-2,3-epoxide via a cytochrome P-450-dependent reaction. Mt. Shasta rainbow trout is the most sensitive species known to the hepatocarcinogenic effects of aflatoxin B1. We have previously isolated and purified a minor form of cytochrome P-450 from this strain of rainbow trout, with a lambda max in the carbon monoxide-reduced difference spectrum of 449.5 nm and a molecular weight of 54,000. In this study, we have compared in a reconstituted system this trout P-450 to trout cytochrome P-448 and rat cytochrome P-450 and P-448 for metabolism and activation of aflatoxin B1. Trout cytochrome P-450 had much higher activity towards aflatoxin B1 and a greater degree of regioselectivity in the formation of aflatoxin B1-2,3-dihydroxy-2,3-dihydrodiol and was much more efficient in producing aflatoxin B1 covalent adducts with DNA. The existence of such a form of cytochrome P-450 in Mt. Shasta rainbow trout may be responsible for the acute sensitivity of this strain to the carcinogenic effects of aflatoxin B1.
D016604:Aflatoxin B1 / Q000031:analogs & derivatives; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D014337:Trout
D000348:Aflatoxins; D003580:Cytochromes; C006426:aflatoxin B1-2,3-oxide; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2