Frequent c-Ha-ras gene mutations in rat mammary carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant h eterocyclic amine in cooked meat and fish, is carcinogenic to the mammary g lands of rats. Mutations in the H-ras gene were here examined in PhIP-induc ed mammary tumors of female F344 rats by the polymerase chain reaction foll owed by single strand conformation polymorphism analysis (PCR-SSCP) and res triction enzyme length polymorphism analysis (RFLP). Mutations in codon 12 of the H-ras gene were detected in four out of 13 tumors by PCR-SSCP. Three of them were GGA to GAA, and one was GGA to GTA. However, by RFLP analysis , four additional mutations in codon 13 were also detected in the same samp les. Two had a GGC to CGC mutation, and the other shifts were GGC to GAC an d GGC to GTC. Therefore, overall eight out of 13 cases had H-ras gene mutat ions. These results indicate that changes in H-ras function may play import ant roles in PhIP-induced mammary carcinogenesis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.