Prevention of Oral Cancer by Tea: A mechanism Study

啮齿动物的机制和肿瘤生物测定研究都提供了强有力的证据支持 茶在预防各种癌症方面的潜力。然而，迄今为止，流行病学研究 关于茶叶消费和人类癌症发病率下降的数据不一致。在 为了验证实验室的研究，我们认为，重要的是进行研究的机制，茶 在临床环境中预防癌症发生。一项干预研究报告说，茶可以防止 吸烟者口腔组织癌前病变的发展。这一发现提供了一个独特的机会， 用于研究茶在人类中预防癌症的机制。在这个提案中，我们的目标是阐明 以吸烟者口腔细胞为模型，探讨茶预防癌症的分子机制。我们 假设香烟烟雾中致癌物引起氧化和其他特异性DM损伤， 导致吸烟者口腔癌。这一过程可被茶多酚类化合物和咖啡因抑制 通过它们作为抗氧化剂和/或致癌物代谢酶的调节剂的活性， p53的诱导剂，其导致细胞生长抑制或凋亡。为了验证这些假设，我们将收集 吸烟者和非吸烟者的口腔细胞作为对照，用于以下目的中提出的研究：目的1， 为了确定茶是否抑制两种主要类型的氧化DNA损伤的形成，8-羟基- 目的2、研究茶叶对烯醛和脱氧鸟苷的影响， 目的3、研究茶叶对烟草致癌物代谢的影响， 目的4，确定茶是否诱导生长停滞或凋亡 通过p53途径。这些研究将阐明抑制吸烟者口腔癌的机制 并验证饮茶对人类癌症的保护作用。

Both mechanism and tumor bioassay studies in rodents have provided strong evidence supporting the potential of tea in the prevention of various cancers. However, epidemiological studies have so far generated inconsistent data regarding tea consumption and decreased incidences of human cancers. In order to verify the laboratory studies, we believe it is important to carry out studies on the mechanisms of tea in the prevention of carcinogenesis in a clinical setting. An intervention study reported that tea prevents the development of preneoplastic lesions of oral tissue in smokers. This finding provides a unique opportunity for the study of mechanisms of cancer prevention by tea in humans. In this proposal, our goal is to elucidate the molecular mechanisms of cancer prevention by tea using oral cells of smokers as a model. We hypothesize that oxidative and other specific DMAdamage caused by carcinogens in cigarette smoke can lead to oral cancer in smokers. This process can be inhibited by tea polyphenolic compounds and caffeine through their activities as antioxidants and/or modulators of enzymesfor carcinogen metabolism and as inducers of p53 which results in cell growth inhibition or apoptosis. To test these hypotheses, we will collect oral cells from smokers and non-smokers, as controls, for the studies proposed in the following Aims: Aim 1, to determine whether tea inhibits the formation of two major types of oxidative DNAdamage,8-hydroxy- deoxyguanosine and the enal-derived cyclic adducts; Aim 2, to study the effectsof tea on the enal and glutathione levels in oral cells; Aim 3, to study the effects of tea on metabolism of tobacco carcinogens and the formation of their DNA adducts; and Aim 4, to determine whether tea induces growth arrest or apoptosis via p53 pathways. These studies will elucidate the mechanisms for the inhibition of oral cancer insmokers by tea and verify the protective role of tea drinking against human cancers.