Carcinogens with diverse mutagenic activities initiate neoplastic guinea pig cells that acquire the same N-ras point mutation

N-ras has been identified by molecular cloning and DNA sequence analysis as the activated oncogene in carcinogen-induced guinea pig transformation. The deduced guinea pig amino acid sequence differs from that of human and mouse by 1 and 4 residues, respectively; the mismatches were in the C-terminal half of the fourth exon. The activated N-ras clone has an AT to TA transversion at the third position of codon 61 which results in the insertion of histidine instead of glutamine. The same activated N-ras gene with the identical mutation was found in all lines regardless of initiating carcinogen (aromatic aryl hydrocarbons or alkylating agents). These results suggest that the mutational event was independent of the mutagenic activity of the initiating carcinogen.