Green tea effects on gene expression in tobacco users

描述（由申请人提供）：绿茶（GT）是一种主要由儿茶素（酚类黄酮）和咖啡因组成的混合物，在啮齿类动物中显示出预防肺癌和许多其他自发和实验诱导的癌症的功效。除了含有可以直接灭活致癌物质的抗氧化剂外，GT还显示出在体外诱导癌细胞凋亡、导致细胞周期阻滞和影响大量调节蛋白的能力。尽管证据存在争议，但食用GT与减少人类癌症（如肺癌、前列腺癌和胃肠道癌症）有关。这可能是由于人类癌症的潜伏期长，缺乏相关GT靶点的知识，以及难以监测长期GT摄入量。我们的初步研究是通过非侵入性地从人类吸烟者身上获取细胞，结果表明，至少在一些人身上，GT可以逆转致癌物质暴露的一些早期影响——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对潜在的化学预防进行评估而变得困难。有必要及早确定个体受试者的预防活动，以便例如优化药物的使用频率。虽然这在啮齿动物研究中是可行的，但在人类受试者中反复进行组织活检来评估变化是不太可以接受的。我们已经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，然后显著地证明，以这种无创、无痛的方式获得的细胞适用于蛋白质检测。我们和其他人最近已经证明，这种方法可以用于观察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以用来确定每天5杯GT对空气消化癌高危人群（吸烟者）上皮细胞功能的影响。这种方法有可能显示GT如何抑制肿瘤的形成。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，它可以用于快速识别可能的个体

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.