N-hydroxylation of carcinogenic and mutagenic aromatic amines.

نویسندگان

  • R Kato
  • T Kamataki
  • Y Yamazoe
چکیده

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.

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عنوان ژورنال:
  • Environmental Health Perspectives

دوره 49  شماره 

صفحات  -

تاریخ انتشار 1983