Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon

The metabolic activation of the food-borne rodent carcinogens 2-amino-3-methylimidazo [4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo [4,5-f]quinoline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-bpyridine (PhIP) and 2-amino-6-methyldlpyrido{1 ,2-a :3' ,2'-d]imidazole (Glu-P-1) was compared with that of the known human carcinogen 4-aminobiphenyl (ABP), using human liver microsomes, human and rat liver cytosols, and human colon cytosol. All of these aromatic amines were readily activated by N-hydroxylation with human liver microsomes (2.3–5.3 nmol/min/mg protein), with PhIP and ABP exhibiting the highest rates of cytochrome P450IA2-dependent N-oxidation, followed by MeIQ IQ and Glu-P-1. In contrast, while ABP and 2-aminofluorene were readily N-acetylated (1.7–2.3 nmol/min/mg protein) by the polymorphic human liver cytosolic N-acetyltransferase, none of the heterocyclic amines were detectable as substrates (