DNA Cleavage and its Mechanism by Vanadyl-1, 10-Phenanthroline Derivatives in the Presence of Hydrogen Peroxide

Abstract

Vanadium complexes have been proposed to show antineoplastic activity. Among them, a newly synthesized 1 : 1 vanadyl-1, 10-phenanthroline(VO (phen)) complex has been found to have a characteristic antitumor activity in vitro experiments. To know the mechanism, we investigated the reactivity of VO complex with substituted phenanthroline for DNA. The VO (phen) derivatives induced DNA cleavage effectively in the presence of hydrogen peroxide. Lineweaver-Burk plots for the complex binding to calf thymus DNA suggested that the VO (phen) derivatives have high affinities to DNA molecule. To examine the active species for DNA cleavage, ESR spin trapping was performed. Hydroxyl radicals were detectable in VO (phen) derivatives-H₂O₂systems. VO (phen) derivatives are indicated to bind DNA and cleave it with the formation of hydroxyl radicals by a Fenton-like reaction when H₂O₂ is present in the system.