Detection of distinct transforming genes in X-ray induced tumors

DNAs from mouse skin tumors (papillomas, squamous cell carcinomas, basal cell carcinomas and pilomatrixomas) initiated with X-irradiation and promoted with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) demonstrated dominant transforming activity by the production of transformed foci in the mouse recipient line, NIH3T3. Dominant transforming activity was not found in DNA isolated from normal mouse epidermis or from the corresponding liver. The NIH3T3 transformants induced with squamous cell carcinoma DNA grew in soft agar and formed tumors in nude mice. Southern blot analysis of primary NIH3T3 transformant DNAs carrying oncogenes from radiation-initiated squamous cell carcinomas indicated that the oncogenes responsible for the transformation of the recipient cells were not Ha-ras, Ki-ras or N-ras genes, nor were they erbB, B-lym, met, neu or raf. The data presented indicate that DNAs from radiation-initiated mouse skin tumors contain dominant transforming genes that are detectable by DNA-mediated gene transfer. The oncogene sequences activated in these radiation-initiated tumors are distinct non-ras transforming genes.