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(-)-Epigallocatechin gallate (EGCG) is known to be the major bioactive polyphenol in green tea contributing to its cancer chemopreventive effects. Multiple mechanisms by which EGCG and other green tea ingredients can protect against cancer have been described (Toxicol. Lett. 150: 43, 2004). EGCG can modulate cell cycle regulatory proteins and by controlling intracellular signaling cascades EGCG seems to regulate cell growth. As we previously have shown that EGCG can also induce the formation of poly(ADP-ribose) in human lymphocytes (Mutation Research 534: 77, 2003), we suggested that the chemopreventive effect of EGCG may be partly attributed to an interaction with the cellular DNA repair machinery. To further support this notion, we used a customized cDNA array (DNA Repair 1: 237, 2002) and investigated EGCG-induced changes in gene expression in human lymphoblastoid cells of more than 130 human DNA repair or repair-related genes. Data generated by cDNA arrays were verified on 15 selected genes by real-time RT-PCR. Cells were treated with EGCG for 2-48 hours at different concentrations (1-200μM) in culture medium containing 2 or 15% serum (FCS). After treatment with 20μM EGCG at 2% FCS a number of DNA repair and repair-related genes showed a dose-dependent induction of mRNA expression reaching maximal values at 24 hours: c-fos, p21, and TOP3a were up-regulated more than 5-fold; expression of BRCA1, CDKN1C, ERCC5, MPG, POLK1, RAD23A and XPC was 2-4 fold induced. This up-regulation decreased over time but was still detectable after 48 hours. Under the same experimental conditions but with 15% FCS-containing culture medium, no changes in gene expression were observed. At this high FCS content induction of gene expression was only seen at a concentration of ≥ 100μM EGCG, which already decreased cell viability. Our results demonstrate that EGCG is able to induce mRNA expression of a number of DNA repair or repair-related genes in vitro. These data lend support for an interaction of EGCG with cellular DNA repair processes. This in part, may be responsible for the chemopreventive effects of EGCG possibly acting via a more efficient repair of damaged DNA. (work conducted in cooperation with Axaron Bioscience AG, Heidelberg, Germany)

[Proc Amer Assoc Cancer Res, Volume 47, 2006]