Specificity of rat liver cytochrome P-450 isozymes in the mutagenic activation of benzo[a]pyrene, aromatic amines and aflatoxin B1.
The ability of three purified forms of rat liver cytochrome P-450 to metabolically activate benzo[a]pyrene, trans-benzo-[a]pyrene-7,8-dihydrodiol, 2-aminofluorene, aflatoxin B1, dimethylnitrosamine, and a pyrolysis product of tryptophan(3-amino-1-methyl-5H-pyrido(4,3-b)indole) (Trp-P-2) to mutagenic products was examined using Salmonella typhimurium strains TA98 and G46 in a reconstituted monooxygenase system. The isozymes examined were cytochrome P-450-PB (the major phenobarbital inducible form), and the two major 3-MC inducible forms (cytochromes P-448(52) and P-448(55)). Cytochromes P-448(52) and P-448(55) preferentially metabolize 2-aminofluorene and Trp-P-2 to mutagenic products. However, only cytochrome P-448(55) metabolizes benzo[a]pyrene and its 7,8-dihydrodiol derivative to mutagenic products. Both cytochrome P-448(52) and P-448(55) metabolize aflatoxin B1 to mutagenic products at a much faster rate than cytochrome P-450-PB. Dimethylnitrosamine was not activated by any of the isozymes tested.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000588:Amines / Q000378:metabolism*; D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000201:enzymology
D000348:Aflatoxins; D000588:Amines; D001580:Benzopyrenes; D007527:Isoenzymes; D009153:Mutagens; D001564:Benzo(a)pyrene; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D006899:Mixed Function Oxygenases