DNA adduct levels and intestinal lesions in congenic rapid and slow acetylator Syrian hamsters administered the food mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)

Epidemiological studies indicate that rapid acetylators with a high intake of well-done red meat have an increased risk of colorectal cancer. Arylamin e N-acetyltransferase enzymes (E.C. 2.3.1.5) activate carcinogenic heterocy clic amines found in the crust of fried meat via O-acetylation of their N-h ydroxylamines to reactive intermediates that bind covalently to DNA and pro duce mutations. Syrian hamsters as well as humans express two N-acetyltrans ferase isozymes (NAT1 and NAT2) which differ in substrate specificity and g enetic control. Nucleic acid substitutions in the NAT2 gene segregate indiv iduals into rapid, intermediate and slow acetylator phenotypes. In the pres ent paper, Ne examined the role of the polymorphic NAT2 acetylator genotype in carcinogenesis induced by the food mutagens 2-amino-1-methyl-6-phenylim idazo[4,5-b]pyridine (PhIP) or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by comparing Syrian hamster lines congenic at the NAT2 locus. No differenc es were found between rapid and slow acetylator congenic hamsters in levels of intestinal PhIP-DNA adducts. In contrast to previous studies in rats, n o carcinogen-related induction of the preneoplastic lesions aberrant crypt foci or tumors was found in the intestines of rapid and slow acetylator con genic Syrian hamsters administered PhIP or IQ.