Flavonoids are known to have antioxidant activity that may limit DNA damage and help prevent degenerative diseases, including cancer. However, our knowledge of flavonoids' role in DNA protection/repair mechanism(s) is limited. This study investigated the effects of quercetin on DNA oxidation and DNA repair in Caco-2 cells with or without oxidant (H2O2) challenge. Quercetin (1, 100 microM) significantly reduced oxidative DNA damage, as measured by the number of single-strand breaks identified by single cell gel electrophoresis. Quercetin treatment also caused a measurable increase in the mRNA expression of human 8-oxoguanine DNA glycosylase (hOGG1) at 0 and 4h after H2O2 treatment (measured using RT-PCR). In addition, the highest level of quercetin tested (100 microM) maintained hOGG1 expression at basal levels or higher for up to 12h after H2O2 treatment, while oxidant treatment alone resulted in significant reduction of hOGG1 at 8h. Our study indicates that quercetin could protect DNA both by reducing oxidative DNA damage and by enhancing DNA repair through modulation of DNA repair enzyme expression.