Green tea effects on gene expression in tobacco users

描述(申请人提供)：绿茶(GT)是儿茶素(苯酚类黄酮)和咖啡因的主要混合物，已显示出在预防肺癌和其他大量自发和实验诱导的啮齿动物癌症方面的有效性。除了含有可直接灭活致癌物的抗氧化剂外，GT还显示出在很大程度上在体外诱导癌细胞凋亡、导致细胞周期停滞并影响大量调节蛋白的能力。GT的摄入与人类癌症的减少有关，例如肺癌、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。我们的初步研究是从吸烟者身上非侵入性地获得细胞，表明GT可以逆转至少在某些人中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，凋亡率增加。癌症化学预防试验因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。需要及早确定个体受试者中的预防活动，以允许例如优化试剂的使用频率。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是不太能被接受的。我们已经使用口腔刷细胞学从GT消费者那里获得了有活力的口腔上皮细胞，然后显著地证明，以这种非侵入性、无痛的方式获得的细胞适合于蛋白质分析。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，并且我们已经证明了它的重复性。我们的假设是，使用非侵入性方法从口腔中获取的细胞可以用来确定每天摄入5杯GT对患航空消化系统癌症(吸烟者)的高危人群的上皮细胞功能有什么影响。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GT引起的可能与肿瘤抑制相关的变化，它可以用于快速识别可能 从GT消费中受益。

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.