Prevention of Oral Cancer by Tea: A mechanism Study

产品说明： 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，流行病学研究迄今为止产生的关于茶消费和人类癌症发病率下降的数据不一致。为了验证实验室研究，我们认为重要的是在临床环境中对茶预防致癌作用的机制进行研究。一项干预研究报告说，茶可以预防吸烟者口腔组织癌前病变的发展。这一发现为研究茶在人类中预防癌症的机制提供了独特的机会。在这项提案中，我们的目标是以吸烟者的口腔细胞为模型，阐明茶预防癌症的分子机制。我们假设香烟烟雾中致癌物质引起的氧化和其他特异性DNA损伤可导致吸烟者患口腔癌。茶多酚化合物和咖啡因可通过其作为抗氧化剂和/或致癌物代谢酶的调节剂以及作为导致细胞生长抑制或凋亡的p53诱导剂的活性来抑制该过程。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，用于以下目的的研究：目的1，确定茶是否抑制两种主要类型的氧化DNA损伤，8-羟基脱氧鸟苷和烯醛衍生的环加合物的形成;目的2，研究茶对口腔细胞中烯醛和谷胱甘肽水平的影响;目的3研究茶叶对烟草致癌物代谢及其DNA加合物形成的影响;目的4研究茶叶是否通过p53途径诱导烟草生长停滞或凋亡。这些研究将阐明茶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。

DESCRIPTION: 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 DNA damage 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 enzymes for 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 DNA damage, 8-hydroxy- deoxyguanosine and the enal-derived cyclic adducts; Aim 2, to study the effects of 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 in smokers by tea and verify the protective role of tea drinking against human cancers.