N-hydroxylation of carcinogenic and mutagenic aromatic amines.
N-Hydroxylation and mutagenic activation of heterocyclic aromatic amines from protein pyrolysis products were studied in rat liver microsomes and nuclei, rat hepatocytes and various species of purified cytochrome P-450. These mutagenic amines include Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole), Glu-P-1 (2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole), Glu-P-2 (2-amino-dipyrido[1,2-a:3',2'-d]imidazole) and IQ (2-amino-3-methyl-3H-imidazo-[4,5-f]quinoline). The number of revertants of Salmonella typhimurium TA 98 was always correlated to the amount of each of the N-hydroxylated metabolites in various experimental conditions. The N-hydroxylated amines covalently bound to DNA directly or after being acylated with amino acids by amino-acyl-tRNA synthetase. Various species of cytochrome P-450 preparations showed markedly different activity in N-hydroxylation and mutagenic activation of Trp-P-2, Glu-P-1 and IQ. A high spin form of cytochrome P-450, isolated from the liver of PCB-treated rats, showed very high activity in N-hydroxylation of Trp-P-2, Glu-P-1 and 2-aminofluorene, although its activity was very low in benzo(a)pyrene hydroxylation. The present results indicate that different species of cytochrome P-450 are involved in the N-hydroxylation and mutagenic activation of aromatic amines.
D000588:Amines / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D013950:Thymus Gland / Q000378:metabolism
D000588:Amines; D002243:Carbolines; D002273:Carcinogens; D009153:Mutagens; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D004247:DNA; D003577:Cytochrome P-450 Enzyme System