UV-induced DNA damage in humans

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.