Prevention of Oral Cancer by Tea: A mechanism Study

说明： 在啮齿动物身上进行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，流行病学研究得出了关于茶叶消费和人类癌症发病率下降的不一致数据。为了验证实验室的研究，我们认为在临床环境中开展TEA预防致癌机制的研究是很重要的。一项干预研究报告称，茶可预防吸烟者口腔组织癌前病变的发生。这一发现为研究茶预防人类癌症的机制提供了一个独特的机会。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的致癌物引起的氧化和其他特定的DNA损伤可能会导致吸烟者患口腔癌。茶多酚类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p53的诱导剂而抑制这一过程，从而导致细胞生长抑制或细胞凋亡。为了验证这些假说，我们将收集吸烟者和不吸烟者的口腔细胞作为对照，进行以下目的的研究：目的1，确定茶是否能抑制两种主要类型的DNA氧化损伤，8-羟基脱氧鸟苷和肠道衍生的环状加合物的形成；目的2，研究茶对口腔细胞中肠道和谷胱甘肽水平的影响；目的3，研究茶对烟草致癌物代谢和DNA加合物形成的影响；以及目的4，确定茶是否通过P53途径诱导生长停滞或细胞凋亡。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.