AMPLIFICATION OF THE C-MYC ONCOGENE IN RADIATION-INDUCED RAT SKIN TUMORS AS A FUNCTION OF LINEAR ENERGY-TRANSFER AND DOSE

The c-myc oncogene was previously shown to be amplified in large, later- stage carcinomas of the rat skin induced by 0.8-MeV electrons. In a panel of 70 tumors induced by neon ions (45 keV/μm), c-myc amplification was rare, and in contrast to the data for tumors induced by low-linear-energy transfer (LET) (0.3 keV/μm) radiation, showed no correlation with tumor size, growth period, or time, but was associated with radiation dose. The tissue specificity for c-myc amplification seen in tumors induced by electrons was not seen in tumors induced by neon ions. These results suggest that quite distinct molecular mechanisms operate even in late stages of carcinogenesis that depend on the LET of the inducing radiation. Furthermore, the results suggest that c-myc amplification observed in tumors induced by low-LET radiation is not a general property of rat skin carcinomas, but is linked mechanistically to the inducing radiation, even though it is not detectable until many months after exposure and tumor appearance.