The electrochemical oxidation of DNA mediated by [Ru(bpy)(2)tatp](2+) (bpy = 2,2'-bipyridine, tatp = 1,4,8,9-tetra-aza-triphenylene) upon incorporation of [Co(phen)(3)](3+) (phen = 1,10-phenanthroline) has been investigated. The results from emission spectra and fluorescence microscope images suggest the formation of an aggregate containing [Ru(bpY)(2)tatp](2+), DNA and [co(phen)(3)](3+) based on the strong interactions. The evidences from repetitive differential pulse voltammograms and cyclic voltammogams reveal that the presence of [Co(phen)(3)](3+) can promote the oxidation of DNA mediated by [Ru(bpy)(2)tatp](2+) on an indium tin oxide (ITO) electrode. The oxidative response of DNA shows a cumulative enhancement with increasing the voltammetric sweeping number, and a stable linear response to DNA is found between 0.001 mM and 0.1 mM. Furthermore, the oxidative mechanism of DNA mediated by [Ru(bpy)(2)tatp](2+) upon incorporation of [Co(phen)(3)](3+) becomes evident, depending on the concentration of DNA and mediators, the structure of mediators and scan rate. The results from this study provide a significant basis for better understanding the oxidative damage of DNA mediated by DNA-binding agents. (C) 2011 Elsevier B.V. All rights reserved.