DNA strand scission by Fe(III) 2-methylaminopyridine complex and hydrogen peroxide

Oxidative DNA damage is involved in mutagenesis, carcinogenesis, aging, radiation effects and also in the action of several anticancer drugs. Accumulated evidence indicates that iron may play an important role in these processes. The conversion of the closed circular double-stranded supercoiled plasmid pcDNA3 into the nicked circular and linear forms was used to investigate DNA nicking induced by the reactions of an iron complex of 2-methylaminopyridine (L), which exhibited a pronounced superoxide dismutase-mimetic activity and antitumour activity with H2O2. Hence the dose-response curve for the [FeL2Cl2]Cl.H2O-mediated H2O2-dependent DNA nicking was studied. For a fixed concentration of [FeL2Cl2]Cl.H2O (25 microM), the concentration of H2O2 producing a maximum extent of DNA nicking was 100 microM. The effects of these two constituents are synergistic. The biological antioxidants such as glycerol, sodium azide and superoxide dismutase significantly inhibited DNA breakage induced by [FeL2Cl2]Cl.H2O and hydrogen peroxide.