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 un der aerobic conditions. Myricetin induced significant (P < 0.05) conce ntration-dependent nuclear DNA degradation concurrent with lipid perox idation; these effects were enhanced by iron (III) or copper (II). Cat alase, superoxide dismutase (SOD), mannitol and sodium azide did not i nhibit myricetin-induced nuclear DNA damage in the presence of iron (I II) or copper (II). However, all of these antioxidants stimulated myri cetin-induced DNA damage in the presence of copper (II). Lipid peroxid ation induced by myricetin was significantly inhibited only by SOD in the presence of copper (II), whereas it was enhanced by catalase and s odium azide in the presence of iron (III). These results demonstrate t he pro-oxidant properties of polyphenolic flavonoids, which are genera lly considered to be antioxidants and anticarcinogens, and suggest a d ual role for these flavonoids in mutagenesis and carcinogenesis.