Interactions of surface-confined DNA with acid-activated mitomycin C

Abstract

The anti-cancer drug mitomycin C (MC) was acid-activated and its interaction with single-stranded calf thymus DNA, immobilized at the surface of the hanging mercury drop electrode (DNA-modified HMDE) was studied by cyclic voltammetry. It was found that immersion of the DNA-modified electrode in a solution of acid-activated MC (at pH 3.9) for a short time (usually 1 min) at open current circuit, followed by transfer of the electrode in a neutral blank background electrolyte, resulted in a decrease of the anodic peak G (due to guanine residues in DNA) and in the formation of a reversible couple at approx. −0.44 V. The potential of the cathodic peak was approx. 50 mV more negative than the cathodic peak of the acid-activated MC obtained under the same conditions in the absence of DNA. No changes of peak G occurred and only a very small cathodic peak appeared if the DNA-modified electrode was immersed in an MC solution not exposed to acid pH. On the basis of these results and additional experiments, including dependence on concentration, time and pH during the interaction of MC with DNA at the electrode surface, we concluded that acid-activated MC is covalently bound to guanine residues in DNA immobilized at the electrode surface and that the quinone group in the DNA-MC adduct is reversibly reduced at the electrode.