HETEROCYCLIC AROMATIC AMINE METABOLISM, DNA ADDUCT FORMATION, MUTAGENESIS, AND CARCINOGENESIS

Abstract

Heterocyclic aromatic amines (HAAs) are carcinogenic compounds formed in meats, fish, and poultry prepared under common household cooking practices. Some HAAs are also formed in tobacco smoke condensate. Because of the widespread occurrence of HAAs in these daily staples, health concerns have been raised regarding the potential role of HAAs in the etiology of some human cancers associated with frequent consumption of these products. In this review, the metabolism of HAAs to biologically active metabolites that bind to DNA and provoke mutations and cancer in various biological systems is discussed. Some of the current analytical and molecular methods that are used to measure biomarkers of HAA exposure and genetic damage in experimental animal models and humans are also presented. These biochemical data combined may help to better assess the role that HAAs may have in the development of some common forms of human cancers.

Key Words :

• AMS, accelerator mass spectrometry
• AαC, 2-amino-α-carboline
• DMIP, 2-amino-1,6-dimethylimidazo[4,5-b]pyridine
• dG, 2′-deoxyguanosine
• MeIQ, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline
• Glu-P-1, 2-amino-6-methyldipyrido[1,2-a:3′,2′-d]imidazole, Glu-P-2
• 2-aminodipyrido[1,2-a:3′,2′-d]imidazole
• HAAs, heterocyclic aromatic amines
• IQ, 2-amino-3-methylimidazo[4,5-f]quinoline
• MeIQx, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
• PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
• 4,8-DiMeIQx, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline
• LC/ESI-MS/MS, liquid chromatography electrospray ionization tandem mass spectrometry
• O-acetyltransferase, OAT
• P450 1A2, cytochrome P450 1A2
• Trp-P-1, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole
• dG-C8-MeIQx, N-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
• dG-N²-MeIQx, 5-(deoxyguanosin-N²-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
• dG-C8-IQ, N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline
• 5-(deoxyguanosin-N²-yl)-2-amino-3-methylimidazo[4,5-f]quinoline, dG-N²-IQ
• dG-C8-PhIP, N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine