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The role of DNA modifications in carcinogenesis and immunosuppression after exposure of human skin to UV-B radiation


Ultraviolet radiation in sunlight is thought to be responsible for the induction of skin tumors. More recently it appeared that exposure of the skin to ultraviolet B (UVB) radiation also results in systemic suppression of the immune system. The latter effect can contribute to an increase in the number of patients suffering from infectious diseases and skin cancer.
Photon absorption produces reactive intermediates, e.g. triplet excited states, singlet oxygen and free radicals, and is the primary step of the interaction of UVB radiation with skin cells, followed by damage to essential biomolecules, such as DNA. Damage to cellular DNA of the skin has been implicated in photocarcinogenesis and UVB-induced immunosuppression. Our aim is to relate UVB-induced DNA damage and its repair to biological effects resulting from UVB irradiation, such as enhanced expression of relevant mRNA molecules, mutagenesis, modulation of cytokine levels as well as immunosuppression in vivo.
Besides animal models, human keratinocytes will be used. The latter will be derived from sun-protected and frequently sun-exposed skin areas of young and aged individuals, as well as from actinic keratoses and squamous cell carcinomas.
The types of DNA damage and their relative amounts will be measured with biochemical, physico-chemical, and immunochemical techniques. The effect of anti-oxidants on the occurrence of certain types of UVB-induced DNA damage and on the related biological effects will also be assessed. From this information the contribution of certain types of UVB-induced cellular damage to skin cancer and immunosuppression may be resolved. This knowledge will provide a scientific basis for protective or prophylactic measures that may be effective in cancer prevention.

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