Past personal investigations into the deleterious effects of sunlight on skin (viz. sunburn, premature aging, pre-malignant and malignant lesions) resulted in the important new finding that contrary to common beliefs, UVA radiation is neither harmless nor helpful to human skin, instead UVA severely enhances the effects of the sunburning UVB rays. In more recent studies (via Grant No. CA17555-02), it was conclusively determined that this effect is not additive but augmentative. Moreover, it was determined that different wavelengths of UVA possess different photoaugmentative potentialities. Further studies conducted under this grant revealed that tumors could be induced in hairless mice irradiated at the same test site using escalating doses of photoaugmentative radiation within a much shorter period of time than has been previously reported. It immediatedly became apparent that this "rapid tumor induction method" would be most useful for providing a large number of young test animals to study the mechanism of carcinogenesis (specifically genetic, biochemical, and electron microscopic) as well as providing a tremendous opportunity to study the effectiveness of both systemic and topical drugs and agents for the prevention of cancer induction and treatment. Xenon solar-simulating UVB plus UVA radiation in escalating, clinically non-severe doses will be utilized to rapidly induce squamous cell cancers in order to determine: (1) precise histologic and electronic microscopic changes that occur during induction, (2) alterations in chromosomes and cell kinetics during induction (3) effects of known and potential chemotherapeutic drugs and agents during and after the induction of cancers, and (4) effects of immunotherapy in prevention and treatment. Knowledge from these studies will be utilized to: (1) gain better insight into the pathogenesis and treatment of cancer, (2) develop a useful in vivo system for evaluating cancer chemotherapeutic and immunotherapeutic drugs, and (3) determine and develop more effective sunscreening drugs and agents.