Both mechanism and tumor bioassay studies in rodents have provided strong evidence supporting the potential of tea in the prevention of various cancers. However, epidemiological studies have so far generated inconsistent data regarding tea consumption and decreased incidences of human cancers. In order to verify the laboratory studies, we believe it is important to carry out studies on the mechanisms of tea in the prevention of carcinogenesis in a clinical setting. An intervention study reported that tea prevents the development of preneoplastic lesions of oral tissue in smokers. This finding provides a unique opportunity for the study of mechanisms of cancer prevention by tea in humans. In this proposal, our goal is to elucidate the molecular mechanisms of cancer prevention by tea using oral cells of smokers as a model. We hypothesize that oxidative and other specific DMAdamage caused by carcinogens in cigarette smoke can lead to oral cancer in smokers. This process can be inhibited by tea polyphenolic compounds and caffeine through their activities as antioxidants and/or modulators of enzymesfor carcinogen metabolism and as inducers of p53 which results in cell growth inhibition or apoptosis. To test these hypotheses, we will collect oral cells from smokers and non-smokers, as controls, for the studies proposed in the following Aims:
Aim 1, to determine whether tea inhibits the formation of two major types of oxidative DNAdamage,8-hydroxy- deoxyguanosine and the enal-derived cyclic adducts;
Aim 2, to study the effectsof tea on the enal and glutathione levels in oral cells;
Aim 3, to study the effects of tea on metabolism of tobacco carcinogens and the formation of their DNA adducts;
and Aim 4, to determine whether tea induces growth arrest or apoptosis via p53 pathways. These studies will elucidate the mechanisms for the inhibition of oral cancer insmokers by tea and verify the protective role of tea drinking against human cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA113449-05
Application #
7758237
Study Section
Special Emphasis Panel (ZRG1-CDP (01))
Program Officer
Perloff, Marjorie
Project Start
2006-03-16
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2012-01-31
Support Year
5
Fiscal Year
2010
Total Cost
$266,623
Indirect Cost
Name
Georgetown University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Greenspan, Emily J; Lee, Hanjoo; Dyba, Marcin et al. (2012) High-throughput, quantitative analysis of acrolein-derived DNA adducts in human oral cells by immunohistochemistry. J Histochem Cytochem 60:844-53
Dash, Chiranjeev; Chung, Fung-Lung; Rohan, Joy Ann Phillips et al. (2012) A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study. BMC Complement Altern Med 12:96