Activation of c-Ha-ras proto-oncogene by in vitro chemical modification with 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 4-nitroquinoline N-oxide (4NQO).

Chemical modification of a plasmid containing the human c-Ha-ras proto-oncogene (pSVMBras-gpt) in vitro with the ultimate carcinogens N-acetoxy-2-amino-6-methyldipyrido[1,2-a: 3',2'-d]imidazole (N-OAc-Glu-P-1) and N-acetoxy-4-aminoquinoline N-oxide (N-OAc-4AQO) generated an activated oncogene that transformed NIH3T3 cells. As DNA is only cellular macromolecule present in the reactions, the results clearly show that the chemical modification of DNA with carcinogens alone can cause the induction of transformation of mammalian cells.