Green tea effects on gene expression in tobacco users

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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.