Green tea effects on gene expression in tobacco users

绿茶对烟草使用者基因表达的影响

• 批准号: 8570538
• 负责人: Guy Richard Adami
• 金额: $ 7.98万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-13 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8570538
• 关键词: Affect; Antioxidants; Apoptosis; Biological Assay; Biological Markers; Biopsy; Blood; Caffeine; Carcinogen exposure; Carcinogens; Carcinoma; Catechin; Cell Cycle Arrest; Cell Proliferation; Cell physiology; Cells; Cellular Assay; Chemoprevention; Clinical Trials; Consumption; Cytology; DNA Adducts; DNA Damage; DNA Modification Methylases; DNA Repair; Depressed mood; Drug Metabolic Detoxication; Epigallocatechin Gallate; Epithelial Cells; Epithelium; Evaluation; Event; Excision; Exposure to; Flavonoids; Frequencies; Gastrointestinal tract structure; Gene Expression; Gene Expression Profiling; Genes; Genetic Transcription; Goals; Green tea; Hamsters; Human; In Vitro; Individual; Inflammation; Intake; Knowledge; Light; Link; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Methods; Modeling; Molecular; Monitor; Nose; Oral; Oral cavity; Oropharyngeal; Painless; Pathway interactions; Phenols; Pilot Projects; Prevention; Prostate; Proteins; Punch Biopsy; RNA; RNA analysis; Randomized Controlled Trials; Reproducibility; Rodent; Role; Sampling; Signal Transduction; Smoker; Surrogate Markers; Testing; Tissues; Tobacco; Tobacco smoke; Validation; Work; angiogenesis; base; cancer cell; cancer chemoprevention; cancer prevention; carcinogenesis; cell injury; drinking; gallocatechol; genetic regulatory protein; high risk; human subject; in vivo; mouse model; oral tissue; polyphenol; prevent; public health relevance; respiratory; tobacco exposure; tumor

DESCRIPTION (provided by applicant): Green tea (GT) is a mixture largely of catechins, which are phenol flavonoids, and caffeine, that has shown efficacy in preventing lung cancer and a large host of other spontaneous and experimentally induced cancers in rodents. In addition to containing antioxidants that can directly inactivate carcinogens, GT has shown the ability, largely in vitro, to induce apoptosis in cancer cells, cause cell cycle arrest and affect large numbers of regulatory proteins. GT consumption has been linked to reductions in human cancers such as those of the lung, prostate, and GI tract, though the evidence is controversial. This may be due to the long incubation period for human cancer, the lack of knowledge of relevant GT targets and the difficulty in monitoring long-term GT intake. Our pilot study, which noninvasively obtained cells from human smokers, showed GT can reverse some of the early effects of carcinogen exposure at least in some people - resulting in fewer cells with DNA damage, lower cell proliferation rates, and increased rates of apoptosis. Cancer chemoprevention trials are made difficult by the need to wait many months or years before the potential chemoprevention can be evaluated. There is a need for early determination of prevention activity in individual subjects to allow, for example, optimization of frequency of consumption of the agent. While this is feasible in rodent studies, taking repeated tissue biopsies to evaluate changes in human subjects is less acceptable. We have used oral brush cytology to obtain viable oral epithelial cells from GT consumers, and then demonstrated, remarkably, that cells obtained in this noninvasive, painless manner were suitable for protein assays. We, and others, have shown recently that this method can be adapted to look at RNA and gene expression, and we have demonstrated its reproducibility. Our hypothesis is that cells obtained from the mouth using noninvasive methods can be used to determine what 5 cups per day GT consumption does to epithelial cell function in humans who are at high risk to get aero-digestive cancers (tobacco smokers). This approach has the potential to show how GT may inhibit tumor formation. By providing a testable method to detect GT induced changes that may be associated with tumor inhibition, it may be used to rapidly identify individuals who will likely benefit from GT consumption.

描述（由申请人提供）：绿茶（GT）是主要由儿茶素（酚黄酮类化合物）和咖啡因组成的混合物，已显示出在啮齿类动物中预防肺癌和许多其他自发性和实验诱发的癌症的功效。除了含有可以直接灭活致癌物的抗氧化剂外，GT 在体外还显示出诱导癌细胞凋亡、导致细胞周期停滞并影响大量调节蛋白的能力。尽管证据存在争议，但摄入 GT 与肺癌、前列腺癌和胃肠道癌等人类癌症的减少有关。这可能是由于人类癌症的潜伏期较长、缺乏对相关GT靶点的了解以及难以监测长期GT摄入量。我们的初步研究以非侵入性方式从人类吸烟者身上获取细胞，结果表明 GT 可以逆转致癌物质暴露的一些早期影响，至少对某些人来说是这样——导致 DNA 损伤的细胞减少，细胞增殖率降低，细胞凋亡率增加。癌症化学预防试验变得困难，因为需要等待数月或数年才能评估潜在的化学预防。需要早期确定个体受试者的预防活性，以允许例如优化药剂的消耗频率。虽然这在啮齿动物研究中是可行的，但通过重复组织活检来评估人类受试者的变化则不太可接受。我们使用口腔刷细胞学从 GT 消费者那里获得活的口腔上皮细胞，然后显着地证明，以这种无创、无痛的方式获得的细胞适合用于蛋白质测定。我们和其他人最近表明，这种方法可以适用于观察 RNA 和基因表达，并且我们已经证明了其可重复性。我们的假设是，使用非侵入性方法从口腔获得的细胞可用于确定每天 5 杯 GT 摄入量对罹患空气消化癌高风险人群（吸烟者）的上皮细胞功能有何影响。这种方法有可能展示 GT 如何抑制肿瘤形成。通过提供一种可测试的方法来检测可能与肿瘤抑制相关的 GT 诱导的变化，它可用于快速识别可能会出现以下情况的个体： 受益于 GT 消费。