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

The anti-cancer drug mitomycin C (MC) was acid-activated and its interactio n with single-stranded calf thymus DNA, immobilized at the surface of the h anging mercury drop electrode (DNA-modified HMDE) was studied by cyclic vol tammetry. It was found that immersion of the DNA-modified electrode in a so lution 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 b lank background electrolyte, resulted in a decrease of the anodic peak G (d ue 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 m ore 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 a nd only a very small cathodic peak appeared if the DNA-modified electrode w as 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 residu es in DNA immobilized at the electrode surface and that the quinone group i n the DNA-MC adduct is reversibly reduced at the electrode. (C) 1998 Elsevi er Science B.V. All rights reserved.