Changes in lifestyle have led to a significant augmentation in the amount of UV radiation that many people receive. Acute UV overexposure causes sunburn; more chronic exposure leads to basal cell and squamous cell carcinoma, melanoma, photoaging and immune suppression. Although sunscreens have provided some benefit in protecting against actinic keratoses and squamous cell carcinomas, their efficacy is modest. It is therefore clear that other chemopreventive agents, that have mechanisms of action that are distinct from sunscreens, are needed to retard the increasing incidence of UV damage to the skin and skin cancer. Green tea polyphenols and, in particular, (-)-epigallocatechin- 3-gallate (EGCG), afford significant protection against the UVB-induced (290- 20 nm) sunburn reaction, sunburn cell formation, immunosuppression and skin cancer. My studies have shown that these agents have a synergistic effect on IL-12 production and that they reduce the number of cyclobutane pyrimidine dimers, a marker of DNA damage. The studies in this proposal will explore the hypothesis that the cancer preventing effects of EGCG occur, at least in part, by augmenting the repair of UV-damaged DNA. I wish to determine whether treatment with EGCG from green tea prevents UVB-induced DNA damage in vitre and, if so, whether it does so through the induction of UV-induced damage of DNA repair enzymes. Those studies will be followed by experiments in which the influence of EGCG on DNA repair is examined in vivo. Finally, because IL-12 has been shown to augment UV-induced DNA repair enzymes, I will evaluate whether IL- 12 is an intermediary in EGCG-induced DNA repair enzyme induction. The results may lead to the generation of new knowledge by which green tea polyphenols exert their chemopreventive effects and hopefully will identify new methods for the prevention of sunlight-related skin disorders including non-melanoma skin cancer.
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