Cytotoxic and mutagenic response of mismatch repair-defective human cancer cells 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 in three human cancer cell lines possessing different mismatch repair (MMR) defects and in matched cell lines corrected for the MMR deficiencies by specific chromosome transfer. Cells deficient in MMR were more resistant to PhIP-induced cytotoxicity and displayed approximately 3-fold more induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus. These results suggest that defects in MMR carried by patients with hereditary nonpolyposis colorectal cancer syndrome may result in enhanced sensitivity to certain dietary and environmental carcinogens such as PhIP.
Glaab
W E
WE
Department of Genetic and Cellular Toxicology, Merck Research Laboratories, West Point, PA 19486, USA. warren_glaab@merck.com
Skopek
T R
TR
D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D005504:Food Analysis; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007093:Imidazoles / Q000493:pharmacokinetics / Q000633:toxicity*; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D009154:Mutation; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D007041:Hypoxanthine Phosphoribosyltransferase