Green Tea: Photodermatological Effects on UV DNA Damage

描述（由申请人提供）：生活方式的改变导致许多人接受的紫外线辐射量显着增加。急性紫外线过度照射会导致晒伤;更长期的照射会导致基底细胞和鳞状细胞癌、黑色素瘤、光老化和免疫抑制。尽管防晒霜在预防光化性角化病和鳞状细胞癌方面提供了一些益处，但它们的功效是适度的。因此，很明显，需要具有不同于防晒剂的作用机制的其他化学预防剂来延缓对皮肤的UV损伤和皮肤癌的增加的发生率。绿色茶多酚，特别是（-）-表没食子儿茶素， 3-没食子酸酯（EGCG），对UVB诱导的（290- 20 nm） 晒伤反应、晒伤细胞形成、免疫抑制和皮肤癌。我的研究表明，这些药物对IL-12的产生有协同作用，并且它们减少了环丁烷嘧啶二聚体的数量，这是DNA损伤的标志。本提案中的研究将探索以下假设：EGCG的癌症预防作用至少部分是通过增强UV损伤DNA的修复而发生的。我希望确定用来自绿色茶的表没食子酸酯（EGCG）处理是否可以预防紫外线B诱导的维特雷中DNA损伤，如果是的话，它是否通过诱导紫外线诱导的DNA修复酶损伤来做到这一点。这些研究之后将进行实验，其中在体内检查EGCG对DNA修复的影响。最后，由于IL-12已被证明能增强紫外线诱导的DNA修复酶， 将评估IL- 12是否是EGCG诱导的DNA修复酶诱导的中介。这些结果可能会导致新知识的产生，通过这些知识，绿色茶多酚发挥其化学预防作用，并有望确定预防日光相关皮肤疾病（包括非黑色素瘤皮肤癌）的新方法。

DESCRIPTION (provided by applicant): 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.