Interactions of flavonoids, trace metals, and oxygen: nuclear DNA damage and lipid peroxidation induced by myricetin.

The extent of DNA damage and lipid peroxidation induced by myricetin, a polyphenolic flavonoid, were studied in isolated rat liver nuclei under aerobic conditions. Myricetin induced significant (P < 0.05) concentration-dependent nuclear DNA degradation concurrent with lipid peroxidation; these effects were enhanced by iron (III) or copper (II). Catalase, superoxide dismutase (SOD), mannitol and sodium azide did not inhibit myricetin-induced nuclear DNA damage in the presence of iron (III) or copper (II). However, all of these antioxidants stimulated myricetin-induced DNA damage in the presence of copper (II). Lipid peroxidation induced by myricetin was significantly inhibited only by SOD in the presence of copper (II), whereas it was enhanced by catalase and sodium azide in the presence of iron (III). These results demonstrate the pro-oxidant properties of polyphenolic flavonoids, which are generally considered to be antioxidants and anticarcinogens, and suggest a dual role for these flavonoids in mutagenesis and carcinogenesis.