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Green tea polyphenols (GTPs) are strong antioxidants and have been found to be antimutagenic and anticarcinogenic in many experimental models and a few human epidemiologic studies. In previous phase IIa intervention study, we found that GTPs at 500 mg and 1,000 mg per day significantly decreased urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), an oxidative DNA damage biomarker, in high-risk residents for liver cancer. To further evaluate the efficacy of GTPs and validate GTP metabolism, we have measured 8-OHdG and GTP components in 700 urine samples collected from a long-term intervention study with 500 mg GTPs per day in 1,800 residents in southern Guangxi, China. Urinary 8-OHdG and GTP components were measured by HPLC-electrocoularray detection. No urinary GTP components were detectable in the placebo group over 12 months (n=350). However, there were significant increases in both urinary (-)-epigallocatechin (EGC) and (-)-epicatechin (EC) levels in the GTP treated group with the averaged values (mean ± SE) of 0.0 ± 0.0, 359.5 ± 45.1, 431.3 ± 75.6, 828.1 ± 121.2, and 1144.0 ± 144.4 ng/mg creatinine for EGC plus EC at 0 (baseline), 1-, 3-, 6-, and 12-month (p<0.001, mixed-effects model), respectively. Conjugated GTPs were the predominant forms for both EGC and EC in urine (> 93%) with glucuronide conjugates accounting for ~ 60% of the totally excreted GTPs. The 8-OHdG levels kept constant in the placebo group over the 12-month period with the averaged levels (mean ± SE) at 10.1 ± 0.8, 10.1 ± 0.9, 9.8 ± 0.8, 10.0 ± 0.8, and 10.1 ± 0.7 ng/mg creatinine, respectively. The 8-OHdG levels in the GTP treated group were significantly decreased with the averaged levels at 10.3 ± 0.8, 8.5 ± 0.7, 7.6 ± 0.5, 6.3 ± 0.3, 6.5 ± 0.3 ng/mg creatinine for 0 (baseline), 1-, 3-, 6-, and 12- month, respectively. Significant dose- (p< 0.001, mixed-effects model) and time- (p< 0.05, mixed-effects model) dependent diminution were observed in the GTP treated group. Results from this study indicate significant increase of GTP components and metabolites in the human body after the long-term intervention. Conjugated EGC and EC are the major forms for urinary excretion. Moreover, this study confirms that GTPs effectively reduced the oxidative DNA damage biomarker, which may have a protective effect against viral- and chemical-induced oxidative stress in human hepatocarcinogenesis. (Supported by the NCI research grant CA90997).

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA