Lipid peroxidation and dna damage induced by morin and naringenin in isolated rat liver nuclei

The pro-oxidant activities, as determined by lipid peroxidation and DNA strand breaks, of morin and naringenin, two polyphenolic flavonoids with molecular structures similar to quercetin, were investigated under aerobic conditions in a model system of isolated rat liver nuclei. Both flavonoids induced a concentration-dependent peroxidation of nuclear membrane lipids concurrent with DNA strand breaks. These reactions were enhanced by the metal ions iron or copper. Active oxygen scavengers catalase, superoxide dismutase and mannitol had no effect on the flavonoid-induced nuclear DNA damage in the presence of the metal ions; nuclear lipid peroxidation was partially inhibited only by mannitol. It appears that hydroxyl radicals are the initiators of the peroxidation of nuclear membrane lipids, producing peroxidation products such as peroxyl radicals that in turn may be responsible for the DNA strand breaks. Alternatively, the hydroxyl radicals produced close to the DNA backbone may induce direct site-specific strand breaks that are insensitive to the free radical scavengers. These results demonstrate the pro-oxidant activities of polyphenolic flavonoids, which are generally considered as antioxidants and anticarcinogens, and suggest their possible dual role in mutagenesis and carcinogenesis.