Analysis of transforming genes in indirectly induced radiogenic thymomas in mice.

The expression of oncogenes was studied in 12 types of 178 mouse tumors induced by radiations and chemicals. DNA was analyzed in tumors in which the overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not in sarcomas induced by radiation. Activation of oncogenes by small mutations and the inactivation of tumor suppressor genes has to be taken in account in the radiation induction of mouse tumors. We therefore made further analyses of radiogenic thymomas. Loss of heterozygocity was revealed in directly induced thymomas by the deletions of allele specific minisatellite bands. Analysis of a hypervariable minisatellite locus also revealed that these thymoma cells suffered high recombinogenic activity during tumorigenesis. In addition, transfection of cellular DNA to normal Golden hamster cells identified the activated K-ras oncogene in the directly induced radiogenic thymomas. Indirectly induced radiogenic thymomas were tested similarly. Transformed cells from secondary transfection experiment were positive for the mouse-specific repetitious sequences, but devoid of mouse ras oncogenes. Indirectly induced radiogenic thymomas originate from unirradiated normal thymus cells transplanted in irradiated hosts. The spontaneous activation of oncogenes yet to be identified may therefore be involved in the development of this tumor.