Prevention of Oral Cancer by Tea: A mechanism Study

茶预防口腔癌：机制研究

基本信息

批准号：
7559962
负责人：
FUNG-LUNG CHUNG
金额：
$ 28.42万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-16 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7559962
关键词：
8-Oxo-2&apos -Deoxyguanosine 8-hydroxy-2&apos -deoxyguanosine Address Agreement Animals Antioxidants Apoptosis Benzo(a)pyrene Biological Assay Black Tea Butanones Caffeine Carcinogen Metabolism Carcinogens Cell Proliferation Cells Clinical Conflict (Psychology)Consumption Control Groups Controlled Study Cultured Cells DNA DNA Adduction DNA Adducts DNA Damage DNA lesion Data Deoxyguanosine Development Doctor of Philosophy Double-Blind Method Drug Metabolic Detoxication Enzymes Epidemiologic Studies Epigallocatechin Gallate Glutathione Goals Green tea Growth Harvest Hepatic Host Defense Human Hydroxyl Radical Incidence Intervention Studies Intervention Trial Laboratory Animals Laboratory Study Lead Lesion Lipid Peroxidation Liver Lung Lung Neoplasms Malignant Neoplasms Mechanics Metabolic Activation Metabolism Methods Modeling Molecular Mouth Neoplasms Mus Nicotine Oral Oral mucous membrane structure Oxidants Pathway interactions Phase Placebos Play Prevention Process Randomized Rattus Reaction Reactive Oxygen Species Reporting Research Personnel Risk Rodent Role Site Smoker Smoking TP53 gene Tea Testing Tissues Tobacco-Associated Carcinogen Water adduct cancer prevention carcinogenesis cell growth cell injury cigarette smoking drinking enzyme activity high risk human CYP2B6 protein human subject malignant mouth neoplasm non-smoker oral cancer prevention oral carcinogenesis oral tissue oxidative DNA damage polyphenol prevent programs protective effect repaired response tool treatment duration treatment effect tumor

项目摘要

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.

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。但迄今为止，流行病学研究产生了关于茶叶消费和人类癌症发病率降低的不一致数据。在为了验证实验室研究，我们认为对茶的作用机制进行研究非常重要在临床环境中预防癌变。一项干预研究报告称，茶可以预防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预防人类癌症的机制。在本提案中，我们的目标是阐明以吸烟者口腔细胞为模型，研究茶预防癌症的分子机制。我们假设香烟烟雾中的致癌物质引起的氧化和其他特定的 DMA 损伤可以导致吸烟者口腔癌。这个过程可以被茶多酚化合物和咖啡因抑制通过它们作为致癌物代谢酶的抗氧化剂和/或调节剂的活性以及 p53 诱导剂，导致细胞生长抑制或凋亡。为了检验这些假设，我们将收集来自吸烟者和非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，确定茶是否能抑制两种主要类型的氧化性 DNA 损伤 8-羟基- 的形成脱氧鸟苷和烯醛衍生的环状加合物；目标2，研究茶对内分泌的影响口腔细胞中的谷胱甘肽水平；目标3，研究茶对烟草致癌物质代谢的影响 DNA加合物的形成；目标 4，确定茶是否会诱导生长停滞或细胞凋亡通过 p53 途径。这些研究将阐明吸烟者抑制口腔癌的机制通过对茶的研究，验证了饮茶对人类癌症的保护作用。