ras Oncogene activation in mammary carcinomas induced by n ‐methyl‐ n ‐nitrosourea in copenhagen rats

The occurrence of Ha‐ ras and Ki‐ ras oncogenes was investigated in mammary tumors produced by treating genetically resistant Copenhagen (Cop) rats with N ‐methyl‐ N ‐nitrosourea. G 35 A codon 12 mutations in both Ha‐ ras and Ki‐ ras genes were analyzed by a polymerase chain reaction/liquid hybridization and gel retardation assay. More than half of the adenocarcinomas analyzed contained an activated Ha‐ ras gene. This was also the predominant mutation in similar tumors from susceptible Buf/N rats, suggesting a common mechanism of initiation. In contrast, only two of 15 mammary adenosquamous carcinomas from the Cop rats contained an activated Ha‐ ras gene, suggesting a different initiation mechanism for most of these tumors. Ki‐ ras activation was found in none of five and one of five adenocarcinomas from Buf/N and Cop rats, respectively, and in none of 13 adenosquamous carcinomas from Cop rats. These results suggest that Ki‐ ras activation does not play a major role in the initiation of the mammary tumors. © 1992 Wiley‐Liss, Inc.