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：
7209014
负责人：
FUNG-LUNG CHUNG
金额：
$ 33.9万
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/7209014
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 Rate 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 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

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.

描述：啮齿动物的机制和肿瘤生物测定研究都提供了有力的证据，这些证据支持茶的潜力预防各种癌症。然而，到目前为止，流行病学研究已经产生了有关茶消耗和人类癌症发生率降低的数据。为了验证实验室研究，我们认为在临床环境中预防茶的机制进行研究很重要。一项干预研究报告说，茶可以防止吸烟者口腔组织的肿瘤性病变的发展。这一发现为研究人类茶预防癌症预防机制提供了独特的机会。在此提案中，我们的目标是使用吸烟者的口腔细胞作为模型来阐明通过茶预防癌症的分子机制。我们假设由烟雾中的致癌物造成的氧化和其他特异性DNA损伤会导致吸烟者的口腔癌。茶多酚化合物和咖啡因可以通过其作为致癌代谢酶的抗氧化剂和/或调节剂的活性来抑制此过程，并作为p53的诱导剂，从而导致细胞生长抑制或凋亡。为了检验这些假设，我们将从吸烟者和非吸烟者中收集口腔细胞，作为对照，以下针对以下目的的研究：目标1，以确定茶是否抑制了两种主要类型的氧化DNA损伤形成，8-羟基脱氧瓜氨酸和enal衍生的环状加成；目的2，研究茶对口腔细胞中烯醇和谷胱甘肽水平的影响；目的3，研究茶对烟草癌代谢的影响及其DNA加合物的形成；目标4，以确定茶是通过p53途径诱导生长停滞还是凋亡。这些研究将通过茶阐明吸烟者抑制口腔癌的机制，并验证饮酒对人类癌症的保护作用。