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Relationship between expression of tumor-specific transplantation antigens and neoplastic transformation in an ultraviolet radiation-induced murine skin cancer.

Ultraviolet radiation-induced murine skin cancers often express highly immunogenic tumor-specific transplantation antigens (TSTA). The relationship between expression of TSTA and neoplastic transformation is not clear. I have used DNA transfection techniques to determine whether expression of TSTA and the transformed phenotype are associated at the genetic level. C3H mouse embryo fibroblast 10T1/2 clone 8 cells were transfected with high-molecular-weight genomic DNA from a highly antigenic ultraviolet radiation-induced 2240 tumor cell line. A cotransfection protocol using pSV2-neo DNA, which confers resistance to the antibiotic G418, was used to select cells that had taken up foreign DNA. Morphologically transformed, G418-resistant colonies were isolated and tested for expression of 2240 tumor-specific antigens by means of a cytotoxic T-lymphocyte assay. None of the 12 morphologically transformed colonies tested expressed 2240 tumor-specific antigens on their cell surface as revealed by their inability to be killed by 2240 tumor-specific cytotoxic T-lymphocytes. In addition, the morphologically transformed cells did not inhibit the killing of 51Cr-labeled 2240 cells by 2240 tumor-specific cytotoxic T-lymphocytes in a cold-target inhibition assay. Cell surface expression of Class I major histocompatibility antigens was not significantly altered in 2240 DNA transformants. These results demonstrate that, in ultraviolet radiation-induced murine skin tumors, there is not coordinate expression of TSTA and the transformed phenotype, even though most ultraviolet radiation-induced skin tumors exhibit both characteristics. This finding suggests that the two phenotypes are controlled by separate genes.