Prevention of Oral Cancer by Tea: A mechanism Study

啮齿类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，到目前为止，流行病学研究已经 产生了关于茶消费和人类癌症发病率下降的不一致数据。在……里面 为了验证实验室的研究，我们认为对茶叶的作用机理进行研究是很重要的 在临床环境中预防癌症的发生。一项干预研究报告称，茶可防止 吸烟者口腔组织癌前病变的发生。这一发现提供了一个独特的机会 用于研究茶预防人类癌症的机制。在这项提议中，我们的目标是澄清 以吸烟者口腔细胞为模型探讨茶叶防癌的分子机制。我们 假设香烟烟雾中致癌物质引起的氧化和其他特异性DMAdamage可以 会导致吸烟者患口腔癌。茶多酚化合物和咖啡因可以抑制这一过程。 通过它们作为抗氧化剂和/或致癌物代谢酶和AS的调节剂的活性 P53的诱导物，导致细胞生长抑制或凋亡。为了检验这些假设，我们将收集 吸烟者和不吸烟者的口腔细胞，作为对照，用于以下目标中提出的研究：目标1， 为了确定TEA是否抑制两种主要类型的氧化DNA的形成，8-羟基-2 目的2，研究茶对小鼠小肠和小鼠小肠运动的影响。 目的3，研究茶叶对烟草致癌物代谢的影响。 它们的DNA加合物的形成；以及目标4，确定茶叶是否诱导生长停滞或细胞凋亡 通过P53通路。这些研究将阐明吸烟者抑制口腔癌的机制。 通过喝茶来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.