The effects of three representative flavonoids, quercetin, myricetin and kaempferol, on the nuclear antioxidant defense glutathione (GSH) and glutathione S-transferase (GST) were investigated in a model system of isolated rat liver nuclei. The three flavonoids induced a concentration-dependent decrease of both the nuclear GSH content and GST activity. Myricetin, which has the maximum number of hydroxyl groups, was the most active. The results demonstrate the pro-oxidant activity of these polyphenolic flavonoids. The impairment of the nuclear antioxidant defense GSH and GST by the polyphenolic flavonoids can lead to oxidative DNA damage, which may be responsible for their mutagenicity.