Cytotoxic and mutagenic response of mismatch repair-defective human cancercells exposed to a food-associated heterocyclic amine

The cytotoxic and mutagenic effects of 2-amino-1-methyl-6-phenylimidazo-[4, 5-b]-pyridine (PhIP), a food-associated heterocyclic amine, were measured i n three human cancer cell lines possessing different mismatch repair (MMR) defects and in matched cell lines corrected for the MMR deficiencies by spe cific chromosome transfer. Cells deficient in MMR were more resistant to Ph IP-induced cytotoxicity and displayed similar to 3-fold more induced mutati ons at the hypoxanthine-guanine phosphoribosyl transferase locus, These res ults suggest that defects in MMR carried by patients with hereditary nonpol yposis colorectal cancer syndrome may result in enhanced sensitivity to cer tain dietary and environmental carcinogens such as PhIP.