Carcinogens heterocyclic aromatic amines

Turesky, R.J. (2004) The role of genetic polymorphisms in metabolism of carcinogenic heterocyclic aromatic amines. Curr. Drug Metab., 5,169-180. 

Turesky, R.J., Lang, N.P., Butler, M.A., Teitel, C.H., and Kadlubar, F.F. (1991) Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. Carcinogenesis, 12, 1839-1845. 

S.D. Mendonsa and R.J. Hurtubise, Capillary electrophoresis (CE) methods for the separation of carcinogenic heterocyclic aromatic amines, J. Liq. Chrom. Rel. TechnoL, 22, 1027-1040, 1999. 

Gross, G. A. and Grliter, A. 1992. Quantitation of mutagenic/carcinogenic heterocyclic aromatic amines in food products. J. Chromatogr. A. 592 271-78. 

Turesky, R. J., Taylor, J., Schnackenberg, L., Freeman, J. P., and Holland, R. D. 2005. Quantitation of carcinogenic heterocyclic aromatic amines and detection of novel heterocyclic aromatic amines in cooked meats and griU scrapings. J. Agric. Food Chem. 53 3248-3258. 

UK Ministry of Agriculture Fisheries and Food and Flealth and Safety Executive, Annual Report of the Working Party on Pesticide Residues in Food (1997), MAFF Publications, London, 1997. lARC, Monographs on the Evabiation of the Carcinogenic Risk of Chemicals to Hnmans Volume 56 Some Naturally Occurring Substances Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins, WFIO, Geneva, 1979, p. 397. 

IARC. Some naturally occurring substances food items and constituents, heterocyclic aromatic amines and mycotoxins. Monographs on the evaluation of carcinogenic risks to humans. 56 489-521, 1993. 

Some Naturally Occurring Substances. Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins (IARC Monographs on the Evaluations of Carcinogenic Risks to Humans), No. 56, International Agency for Research on Cancer, Lyon, 1993, pp. 489-521. 

International Agency for Research on Cancer Some naturally occurring substances Food items, and constituents, heterocyclic aromatic amines and mycotoxins lARC Monogr on the Evaluation of Carcinogenic Risks to Humans. Lyon, World Health Organization, 1993, vol 56. 

Heterocyclic aromatic amines (HAA) are carcinogenic compounds that may occur in food. They are probably formed during cooking processes by the pyrolysis of amino acids and proteins. Since the mid 1990s, LC-MS plays a role in the analysis and characterization of these HAA. Both ESI-MS and APCl-MS are applied. A recent special issne of Journal of Chromatography B [82] emphasizes the analytical challenges related to HAA. The stractnres of the most abundant HAA in cooked food are shown in Figure 14.10. 

Aromatic amines (AAs) and heterocyclic aromatic amines (HAAs) are ubiquitous environmental and dietary contaminants, many of which are carcinogens. Compounds of both classes contain an exocydic amino group, which is a prerequisite for their genotoxicity (Figure 7.1). In this chapter, the sources of exposure, mechanisms of metabolic activation, formation and detection of DNA adducts, and biological effects of AA-DNA and HAA-DNA adducts are highlighted. 

Schwab CE, Huber WW, Parzefall W, Hietsch G, Kassie F, Schulte-Hermann R, KnasmuUer S. Search for compounds that inhibit the genotoxic and carcinogenic effects of heterocyclic aromatic amines. Grit Rev Toxicol 2000 30 1-69. 

Felton, J. S., Fultz, E., Dolbeare, F. A., and Knize, M. G. 1994. Effect of microwave pretreatment on heterocyclic aromatic amine mntagens/carcinogens in fried beef patties. Food Chem. Toxicol. 32 897-903. 

Knize, M. G., Salmon, C. R, Mehta, S. S., and Felton, J. S. 1997b. Analysis of cooked muscle foods for heterocyclic aromatic amine carcinogens. Mutat. Res. 376 129-134. 

Eight heterocyclic aromatic amine carcinogens were extracted from cooked meats. A Cjg column and a complex 30-min 95/5- 45/55 water (lOmM triethylamine phosphate at pH 3.6)/acetonitrile resolved 2-amino-1-methyl-, 2-amino-3,8-dimethyl-, and 2-amino-3,4,8-trimethylimidazo[4,5-/]quinoxaline with monitoring by UV (A = 262 nm) and fluorescence (A = 307 nm, ex 370 nm, em). A 40-min 95/5—>-20/80 water (25 mM triethylamine phosphate at pH 3.6)/acetonitriIe gradient on the same column resolved 2-amino-1,6-dimethylimi-... 

The enzyme can also catalyze the transfer of an acetyl group from an N-acetylated hydroxylamine (hydroxamic acid) to form an acetoxy product, i.e., an N to O transacetylation and this pathway does not require acetyl Co-A (12). A-hydroxy-4-acetylaminobiphenyl provides an example of this conversion as shown in Figure 7.7. The significance of this pathway is that it leads to the activation of the hydroxamic acid because acetoxy derivatives of aromatic amines are chemically reactive and many are carcinogens such as the heterocyclic amines formed when meat is heated to a high temperature, e.g., 2-amino-1-mcthyl-6-phenylirnidaz()[4,5-i ]pyri(linc. 

Both NAT1 and NAT2 N-acetylate benzidine and O-acetylate the N-hydroxy metabolite. Because NAT2 and, to a lesser extent, NAT1 both show variation in the human population, this influences susceptibility to the carcinogenic effects of arylamines such as benzidine. With other aromatic amines, such as the heterocyclic amines found as food pyrolysis degradation products, N-acetylation is not favored, N-oxidation being the primary route followed by O-acetylation. This seems to take place in the colon. 

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