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. 1983 Mar;49:21–25. doi: 10.1289/ehp.834921

N-hydroxylation of carcinogenic and mutagenic aromatic amines.

R Kato, T Kamataki, Y Yamazoe
PMCID: PMC1569125  PMID: 6832094

Abstract

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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Gorrod J. W. Differentiation of various types of biological oxidation of nitrogen in organic compounds. Chem Biol Interact. 1973 Nov;289(303):289–303. doi: 10.1016/0009-2797(73)90004-5. [DOI] [PubMed] [Google Scholar]
  2. Ishii K., Ando M., Kamataki T., Kato R., Nagao M. Metabolic activation of mutagenic tryptophan pyrolysis products (Trp-P-1 and Trp-P-2) by a purified cytochrome P-450-dependent monooxygenase system. Cancer Lett. 1980 Jun;9(4):271–276. doi: 10.1016/0304-3835(80)90017-8. [DOI] [PubMed] [Google Scholar]
  3. Ishii K., Yamazoe Y., Kamataki T., Kato R. Metabolic activation of mutagenic tryptophan pyrolysis products by rat liver microsomes. Cancer Res. 1980 Jul;40(7):2596–2600. [PubMed] [Google Scholar]
  4. Kadlubar F. F., Miller J. A., Miller E. C. Guanyl O6-arylamination and O6-arylation of DNA by the carcinogen N-hydroxy-1-naphthylamine. Cancer Res. 1978 Nov;38(11 Pt 1):3628–3638. [PubMed] [Google Scholar]
  5. Matsukura N., Kawachi T., Morino K., Ohgaki H., Sugimura T., Takayama S. Carcinogenicity in mice of mutagenic compounds from a tryptophan pyrolyzate. Science. 1981 Jul 17;213(4505):346–347. doi: 10.1126/science.7244619. [DOI] [PubMed] [Google Scholar]
  6. Mita S., Ishii K., Yamazoe Y., Kamataki T., Kato R., Sugimura T. Evidence for the involvement of N-hydroxylation of 3-amino-1-methyl-5H-pyrido[4,3-b]indole by cytochrome P-450 in the covalent binding to DNA. Cancer Res. 1981 Sep;41(9 Pt 1):3610–3614. [PubMed] [Google Scholar]
  7. Mita S., Yamazoe Y., Kamataki T., Kato R. Effects of ascorbic acid on the nonenzymatic binding to DNA and the mutagenicity of N-hydroxylated metabolite of a tryptophan-pyrolysis product. Biochem Biophys Res Commun. 1982 Apr 29;105(4):1396–1401. doi: 10.1016/0006-291x(82)90942-1. [DOI] [PubMed] [Google Scholar]
  8. Nagao M., Sugimura T., Matsushima T. Environmental mutagens and carcinogens. Annu Rev Genet. 1978;12:117–159. doi: 10.1146/annurev.ge.12.120178.001001. [DOI] [PubMed] [Google Scholar]
  9. Razzouk C., Mercier M., Roberfroid M. Characterization of the guinea pig liver microsomal 2-fluorenylamine and N-2-fluorenylacetamide N-hydroxylase. Cancer Lett. 1980 Apr;9(2):123–131. doi: 10.1016/0304-3835(80)90116-0. [DOI] [PubMed] [Google Scholar]
  10. Yamazoe Y., Ishii K., Kamataki T., Kato R., Sugimura T. Isolation and characterization of active metabolites of tryptophan-pyrolysate mutagen, TRP-P-2, formed by rat liver microsomes. Chem Biol Interact. 1980 May;30(2):125–138. doi: 10.1016/0009-2797(80)90120-9. [DOI] [PubMed] [Google Scholar]
  11. Yamazoe Y., Kamataki T., Kato R. Species difference in N-hydroxylation of a tryptophan pyrolysis product in relation to mutagenic activation. Cancer Res. 1981 Nov;41(11 Pt 1):4518–4522. [PubMed] [Google Scholar]
  12. Yamazoe Y., Tada M., Kamataki T., Kato R. Enhancement of Binding of N-Hydroxy-TRP-P-2 to DNA by seryl-tRNA synthetase. Biochem Biophys Res Commun. 1981 Sep 16;102(1):432–439. doi: 10.1016/0006-291x(81)91539-4. [DOI] [PubMed] [Google Scholar]

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