J. Biol. Chem., Vol. 262, Issue 8, 3813-3819, Mar, 1987
Carcinogens with diverse mutagenic activities initiate neoplastic guinea pig cells that acquire the same N-ras point mutation
J Doniger, V Notario and JA DiPaolo
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.