Skin cancers are the most common malignancies in humans and have become a major health problem particularly in the Southwestern region of the United States. More than 600000 basal and squamous cell skin cancers and approximately 32000 melanomas were diagnosed in the United States in 1991. The near epidemic rates of skin cancer Incidence are expected to increase even more dramatically In the mid-1990s due to the accelerated loss of ozone from the earth's outer atmosphere. According to NASA officials the levels of chlorine monoxide are high enough to destroy ozone in the Northern hemisphere at the rate of 1-2% per day during late winter 1992 leading to depletion of the Northern ozone layer by 30-40%. Estimates released last february (1992) by the United Nations Environment Program predict a 26% rise in the incidence of non-melanoma skin cancers worldwide if the overall ozone levels drop 10%. Even though the mortality rate from basal cell and squamous cell skin cancers is relatively low they are the source of considerable morbidity and rapidly Increasing health care costs. Additionally melanoma prognosis continues to be poor with mortality rates increasing yearly. Because of the extreme Importance of these public health problems in Arizona we have selected as our overall objective to examine the mechanisms of skin carcinogenesis and develop effective chemoprevention strategies for melanoma and non-melanoma skin cancer. Using specialized research projects various chemopreventive strategies are being tested In order to design and optimize laboratory-based clinical trials in patients with actinic keratoses and resected squamous and basal cell skin cancers. This integrated approach to patients with established and precancerous skin lesions has led to the structure of this Program Project which utilizes novel intermediate markers of skin cancer risk (e.g. bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) labeling Indices mutant Ha-ras gene and p53 gene copy numbers PGE2 and polyamines in actinic keratoses and tissue fatty acids) unique chemopreventive agents (e.g. human melanotropin analogs epigallocatechin gal late or green tea and topically administered agents such as DFMO and moderately high doses of retinyl palmitate) and Innovative biostatistically-based clinical trial designs. The Program Project includes: * Three basic science projects which evaluate immunologic oxidative and genetic mechanisms of skin carcinogenesis. * An epidemiology project which examines unique prognostic factors combined with the extent of UV-B exposure and utilizes up-to-date biologic and chemical marker endpoints. * Three clinical projects which evaluate primary secondary and tertiary chemopreventive strategies in normal subjects and patients with actinic keratosis and resected non-melanoma skin cancers.