The activated human c-Ha-ras-1 oncogene as a mutagen.

The induction of gene mutations and chromosome aberrations by plasmid pEJ6.6 carrying the activated c-Ha-ras-1 oncogene from human bladder carcinoma was studied in cultured Chinese hamster cells. Both an increase in the frequency of hypoxanthine-phosphoribosyltransferase-deficient (HPRT-) mutants and chromosome aberrations was observed after pEJ6.6 transfection as compared to control series (pBR322). In order to define whether it is the oncogene which is responsible for the mutagenic effect of pEJ6.6, a derivative of c-Ha-ras-1 carrying a deletion in its coding region was constructed. As shown in all experiments, the frequency of HPRT- mutants after treatment with pEJ6.6 plasmid exceeded that in control dishes treated by pEJ6.6 plasmid with an inactivated oncogene. The effect was rather weak but statistically significant. Thus, the results of experiments carried out show that the mutagenic activity of pEJ6.6 plasmid is chiefly determined by its oncogene. The role of the mutagenic effects of activated oncogenes in malignant transformation is discussed.