[en] A sample of 12 radiation-induced skin tumors were tested for oncogene activation. Hybridization of the original rat tumor DNA's revealed evidence for c-myc gene amplification and extensive restriction enzyme polymorphisms in 10 of the 12 tumors following digestion with Eco R1, Hind II, and Bam HI. Rehybridization of the filters using probes for the first exon of c-myc, N-myc (first or second exons), v-able and v-myb, showed no differences in band intensity or restriction fragment pattern between tumors and normal rat DNA. Each of 3 clear cell carcinomas, an aggressive, rapidly growing tumor, exhibited activation of both ras and myc oncogenes, while myc alterations alone were observed in 4 out of 5 squamous cell carcinomas. The finding of concurrent multiple oncogene activation is radiation-induced primary tumors provides evidence in favor of the hypothesis that activation of multiple oncogenes contributes to carcinogenesis by ionizing radiation. The mechanism of activation of the c-myc gene (rearrangements and amplification) may reflect the consequences of radiation acting to break the DNA in specific ways