The primary objective of this research project is to study the modulating effects of green tea polyphenols on reducing hepatocarcinogen-induced oxidative damages in high-risk human populations. Oxidative damage induced by reactive oxygen species in vivo plays important roles in human hepatocarcinogenesis primarily caused by chronic infection of hepatitis B/C viruses and exposure to dietary aflatoxins. The level of 8-hydroxy-2'- deoxyguanosine, a biomarker for oxidative DNA damage, increases in hepatitis B virus surface antigen positive and aflatoxin-exposed humans and in aflatoxin- treated animals. Dietary antioxidants are important components of cancer modulating agents, which have been proven to effectively target carcinogen biomarkers, including oxidative damages, in high-risk human populations. Among various identified dietary associated antioxidants, green tea and its polyphenols have been shown to be safe and highly effective in inhibition of a variety of carcinogen-induced oxidative damages, mutagenesis, and tumorigenesis in in vitro bioassays and in vivo animal models. The general hypothesis underlying this proposal is that green tea polyphenols have a protective effect against oxidative stress or damage induced by aflatoxin and hepatitis B/C viruses through the mechanisms of modulating aflatoxin metabolism and oxidated DNA damage.
The specific aims i nclude: (1) to determine antioxidative role of green tea polyphenols in inhibition of the level of 8-hydroxy-2'-deoxyguanosine in urine samples collected from an intervention study of 120 participants who are double positive for hepatitis B virus surface antigen and aflatoxin-albumin adducts, and (2) to determine the modulating effect of green tea polyphenols on excretion of carcinogen detoxifying product, aflatoxin Bl-mercapturic acid in urine samples collected from the study participants. The results of this proposed study will help to understand the mechanisms of antioxidative role of tea polyphenols in modulating human hepatocarcinogenesis caused by hepatitis B/C viruses and aflatoxins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Small Research Grants (R03)
Project #
5R03ES011442-02
Application #
6524836
Study Section
Special Emphasis Panel (ZES1-BKW-C (RO))
Program Officer
Packenham, Joan P
Project Start
2001-09-30
Project End
2003-08-31
Budget Start
2002-09-05
Budget End
2003-08-31
Support Year
2
Fiscal Year
2002
Total Cost
$73,000
Indirect Cost
Name
Texas Tech University
Department
Type
Other Domestic Higher Education
DUNS #
609980727
City
Lubbock
State
TX
Country
United States
Zip Code
79430
Wang, Jincheng; Tang, Lili; Wang, Jia-Sheng (2015) Biomarkers of Dietary Polyphenols in Cancer Studies: Current Evidence and Beyond. Oxid Med Cell Longev 2015:732302
Wang, Jia-Sheng; Luo, Haitao; Wang, Piwen et al. (2008) Validation of green tea polyphenol biomarkers in a phase II human intervention trial. Food Chem Toxicol 46:232-40
Tang, Lili; Tang, Meng; Xu, Li et al. (2008) Modulation of aflatoxin biomarkers in human blood and urine by green tea polyphenols intervention. Carcinogenesis 29:411-7
Luo, Haitao; Tang, Lili; Tang, Meng et al. (2006) Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine. Carcinogenesis 27:262-8