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: 8734356
• 负责人: Guy Richard Adami
• 金额: $ 7.74万
• 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 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8734356
• 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）：绿色茶（GT）是主要由儿茶素（其为酚类黄酮）和咖啡因组成的混合物，其在预防啮齿动物中的肺癌和大量其它自发性和实验诱导的癌症中显示出功效。除了含有可以直接抑制致癌物的抗氧化剂外，GT还显示出在体外诱导癌细胞凋亡、引起细胞周期停滞和影响大量调节蛋白的能力。GT消费与人类癌症的减少有关，如肺癌，前列腺癌和胃肠道癌症，尽管证据存在争议。这可能是由于人类癌症的潜伏期较长，缺乏相关GT靶点的知识以及难以监测长期GT摄入量。我们的初步研究，非侵入性地从人类吸烟者中获得细胞，表明GT可以逆转致癌物暴露的一些早期影响，至少在一些人中-导致DNA损伤的细胞减少，细胞增殖率降低，细胞凋亡率增加。癌症化学预防试验由于需要等待数月或数年才能评估潜在的化学预防而变得困难。需要早期确定个体受试者中的预防活性，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，但在人类受试者中进行重复组织活检以评估变化是不太可接受的。我们已经使用口腔刷细胞学从GT消费者获得活的口腔上皮细胞，然后证明，值得注意的是，在这种非侵入性的，无痛的方式获得的细胞是适合蛋白质测定。我们和其他人最近已经证明，这种方法可以适用于观察RNA和基因表达，我们已经证明了它的可重复性。我们的假设是，使用非侵入性方法从口腔中获得的细胞可用于确定每天5杯GT消费对患有呼吸消化道癌症的高风险人群（吸烟者）的上皮细胞功能的影响。这种方法有可能显示GT如何抑制肿瘤形成。通过提供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，其可用于快速鉴定可能将被诊断为肿瘤的个体。 从GT消费中受益。

项目成果

Gut/Oral Bacteria Variability May Explain the High Efficacy of Green Tea in Rodent Tumor Inhibition and Its Absence in Humans.

• DOI: 10.3390/molecules25204753
• 发表时间: 2020-10-16
• 期刊: Molecules (Basel, Switzerland)
• 作者: Adami GR;Tangney C;Schwartz JL;Dang KC
• 通讯作者: Dang KC

Effects of green tea on miRNA and microbiome of oral epithelium.

• DOI: 10.1038/s41598-018-22994-3
• 发表时间: 2018-04-12
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Adami GR;Tangney CC;Tang JL;Zhou Y;Ghaffari S;Naqib A;Sinha S;Green SJ;Schwartz JL
• 通讯作者: Schwartz JL