INTERACTIONS OF ANTITUMOR DRUG DAUNOMYCIN WITH DNA IN SOLUTION AND ATTHE SURFACE

The interaction of the antitumor drug daunomycin with double-stranded (ds) calf thymus DNA was studied in solution and at the electrode surf ace by means of cyclic voltammetry and particularly by constant-curren t chronopotentiometric stripping analysis (CPSA) with the carbon paste electrodes (CPE), As a result of intercalation of this drug between t he base pairs in dsDNA, the CPSA daunomycin peak delta decreased and a new more positive shoulder delta(b) appeared. This shoulder was attri buted to the oxidation of the drug intercalated in DNA. Under the same conditions almost no changes in the DNA peak G(ox) (due to oxidation of guanine residues) were observed. It was shown that daunomycin adher es strongly to the bare CPE (resisting washing) so that a daunomycin-m odified electrode can be easily prepared. Daunomycin immobilized at CP E interacted with DNA on immersion of the modified electrode into the dsDNA solution, showing a decrease of peak delta and a well-separated peak delta(b) instead of the shoulder (which resulted from the interac tion of DNA with daunomycin in solution). When the DNA-modified CPE wa s immersed into a daunomycin solution the peak G(ox) increased in depe ndence on daunomycin concentration or on the time of interaction of da unomycin with dsDNA at the electrode surface. Such changes in peak G(o x) were observed only at submicromolar concentrations of daunomycin. A t higher daunomycin concentrations or at longer interaction time inter vals a daunomycin peak appeared, which was substantially smaller and m ore positive than the peak of free daunomycin. The increase of the DNA peak G(ox) was attributed to interaction of daunomycin from the side of the DNA double helix not contacting the electrode surface. Such bin ding may induce changes in the DNA structure including bending of the DNA molecule which may result in the increase of peak G(ox), Our resul ts thus suggest that the interaction of daunomycin with DNA anchored a t the surface may significantly differ from that with DNA in solution. The prospects of using of electroanalytical methods in studies of DNA -drug interactions are discussed. (C) 1998 Elsevier Science S.A.