Cytochrome P3-450 cDNA encodes aflatoxin B1-4-hydroxylase.
Aflatoxin B1 (AFB1), a potent hepatocarcinogen and ubiquitous dietary contaminant in some countries, is detoxified to aflatoxin M1 (AFM1) via cytochrome P-450-mediated AFB1-4-hydroxylase. Genetic studies in mice have demonstrated that the expression of AFB1-4-hydroxylase is regulated by the aryl hydrocarbon locus and suggested that different cytochrome P-450 isozymes catalyze AFB1-4-hydroxylase and aryl hydrocarbon hydroxylase activities. We have now examined lysates from mammalian cells infected with recombinant vaccinia viruses containing expressible cytochrome P1-450 or P3-450 cDNAs for their ability to metabolize AFB1 to AFM1. Our results show that cytochrome P3-450 cDNA specifies AFB1-4-hydroxylase. This is the first direct assignment of a specific cytochrome P-450 to an AFB1 detoxification pathway. This finding may have relevance to the dietary modulation of AFB1 hepatocarcinogenesis.
D016604:Aflatoxin B1; D016607:Aflatoxin M1; D000348:Aflatoxins / Q000378:metabolism; D000818:Animals; D002273:Carcinogens; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004274:DNA, Recombinant; D004790:Enzyme Induction / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014616:Vaccinia virus / Q000201:enzymology / Q000235:genetics
D000348:Aflatoxins; D002273:Carcinogens; D004274:DNA, Recombinant; D007527:Isoenzymes; D011083:Polycyclic Compounds; D016607:Aflatoxin M1; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D006899:Mixed Function Oxygenases; C019623:aflatoxin B1 hydroxylase