Ultraviolet radiation (UVR) present in sunlight is known to responsible for the induction of most skin cancers in humans. Since cancers of the skin are the more prevalent form of human cancer, UVR is an important environmental carcinogen. Because of increased exposure to UVR during sunbathing or by the use of tanning salons, it is expected that the morbidity and mortality resulting from skin cancer will become a significant health problem. Studies using mice have shown that UVR induces highly antigenic skin cancers. Recent findings suggest that murine skin cancers induced by UVR have both an individually specific tumor antigen and a UV-associated common antigen. The possible existence of such a common antigen that interacts with cells controlling the tumor rejection response is of considerable significance for immunotherapy and suggests new avenues for immunological intervention in cancer. In addition, the strong antigenicity of UV-induced tumors raises some fundamental questions about the nature of tumor antigens and their relationship to the process of neoplastic transformation. The main objectives of this proposal are: (1) To determine whether UV-associated tumor antigens are associated with neoplastic transformation or can occur independently of the transforming event. (2) To use gene transfer techniques to determine whether UV-associated tumor antigens and neoplastic transformation are associated at the genetic level. Two approaches will be used to address these questions. One involves exposure of cells from spontaneous tumors to UV radiation in vitro to determine whether the UV-associated common antigen can be added on to cells that are already transformed. The second approach is to use DNA transfection techniques to determine whether the transformed phenotype is associated with the expression of a UV-associated antigen. If the two phenotypes result from a single genetic alteration, then selection for cells with the transformed phenotype following DNA transfection should result in the isolation of clones expressing the antigenic characteristics of the donor cells. If antigenicity and transformation represent different effects of UV radiation, then selection for transformed phenotype should not produce clones with the antigenic characteristics of the donor cells.
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