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. G35-->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.