UV-induced DNA damage in humans

Sammanfattning: Ultraviolet radiation is considered to be the most harmful part of solar energy affecting man. The depletion of the ozone layer around the Earth increases the total exposure to UV-light. The incidence of skin cancer in man has been shown to be associated with exposure to solar radiation, especially to UV-light. UV is capable of initiating skin carcinogenesis through DNA damage, particularly by formation of DNA photoproducts. The major products formed by UV irradiation are dipyrimidine compounds, namely cyclobutane dimers and 6-4 photoproducts. A high mutation frequency at pyrimidine sites in skin tumours provides additional evidence for the relationship between UV-induced DNA damage and skin cancer. The research program was focused on the development and application of a highly specific and sensitive 32P-HPLC method for the study of UV-induced DNA damage in humans. ' The application of the developed method to human studies demonstrated that one minimal erythema dose of solar- simulated radiation is capable of inducing levels of DNA damage far exceeding any other known external exposure. This finding may explain the high frequency of skin cancer among other tumours ' There is a large interindividual variation in the induction of photoproducts after exposure to a uniform physical dose of solar-simulated radiation. ' There is no association between erythemal response and induction of DNA damage. ' The reparability of dipyrimidine lesions dependent on the dipyrimidine pair forming a lesion, implicating sequence-specificity of the repair process. ' There is a large interindividual variation in the rates of DNA repair process. Taken all our results together, we have shown that human response to solar- simulated radiation is highly individual. The level of immediate damage may vary for a given acute biological dose and repair rates may vary. At present, we have no evidence that these two aspects are coupled in any way. Thus, a combination of proneness to damage along with poor repair may predispose individuals to skin cancer.