We have developed a system of ultraviolet-light induced transformation of human cells to anchorage-independent growth; we shall study the influence of age and origin of the effects of cell cycle and irradiation schedule, as well as the role of DNA repair and/or misrepair on the transformation frequency. We shall characterize the growth properties, karyotype and tumorigenicity of the transformants. We have developed an alkaline agarose gel electrophoresis method of measuring low levels of pyrimidine dimers in non-radioactive DNA of human skin or cultured cells. We shall measure the action spectrum for pyrimidine dimer formation in human skin. We shall determine whether sunscreening agents and sunlamp radiation sensitize pyrimidine dimer production in human skin. We shall use the gel electrophoresis method to measure DNA repair in human cells and skin; we shall determine the relative roles of excision repair and photoreversal in human skin. We shall measure the action spectrum for dimer reversal to determine if it is mediated by the photoreactivating enzyme. We shall determine the relationship of DNA damage and repair to solar oncogenesis; we shall measure DNA repair in biopsies of normal and of sunsensitive, skin-cancer prone individuals. We shall establish cultures from biopsies of these individuals and shall determine UV transformation frequencies and DNA repair capacities of these cells. We shall assess the ability of in vitro DNA repair measurements to describe accurately in vivo repair rates in man. We shall determine the relationship between in vitro UV-transformation frequencies and propensity to sunlight-induced skin cancer.
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