Specificity of four forms of cytochrome P-450 in the metabolic activation of several aromatic amines and benzo[a]pyrene.
The involvement of four forms of cytochrome P-450 in the activation of the promutagens, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-aminofluorene and 4-aminobiphenyl has been investigated using a Salmonella test system. A high-spin form, P-448 II-a, catalysed the activation of IQ and Glu-P-1 28 and 12 times faster, respectively, than a low-spin form, P-448 II-d, whereas benzo[a]pyrene was metabolized to the phenols 60 times faster by P-448 II-d than P-448 II-a. Both P-448 II-a and P-448 II-d were highly active in the activation of Trp-P-2 and 2-aminofluorene. Treatment of CDF1 mice with polychlorinated biphenyls (PCB) increased the microsomal-activating ability for the promutagens in various degrees. More than a ten-fold increase was observed with Trp-P-2, while the increase was only two-fold with IQ. No sex-related difference was observed for the hepatic microsomal activating ability of male and female CDF1 mice for Trp-P-2, Glu-P-1 or IQ. These results indicate that more than two forms of cytochrome P-450, which are inducible by treatment with PCB or 3-methylcholanthrene, mediate the metabolic activation of heteroaromatic amines in rats and mice.
D000588:Amines / Q000378:metabolism*; D000611:Aminobiphenyl Compounds / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009153:Mutagens / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D011804:Quinolines / Q000378:metabolism
D000588:Amines; D000611:Aminobiphenyl Compounds; D002243:Carbolines; D005449:Fluorenes; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D001564:Benzo(a)pyrene; C012177:2-aminofluorene; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; C014970:2-aminodiphenyl; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls