ELSEVIER Bioelectrochemistry and Bioenergetics 35 (1994) 93-97 Tumour treatment by direct electric current: electrode material deposition Damijan Miklavcic a,*, AleS Fajgelj b, Gregor Sersa c a Faculty of Electrical and Computer Engineering, University of Ljubljana, TrZaSka 25, 61000 Ljubljana, Slovenia b "lozef Stefan" Institute Ljubljana, lamova 39, P.O. Box /00, 61 III Ljubljana, Slovenia C Institute of Oncology, Zaloska 2, 61000 Ljubljana, Slovenia Abstract Direct current electrotherapy was demonstrated to be an effective and relatively inexpensive local treatment of murine solid subcutaneous tumours. The insufficient knowledge of the mechanisms involved hinders its more extensive use in clinical oncology. Attempts were made to establish the correlation between the effectiveness of electrotherapy and deposition of the electrode material in the tumours. Electrotherapy was performed as a 1 h single-shot treatment in different electrode (gold) configurations, one electrode inserted in the tumour being the anode and its pair subcutaneously in the vicinity of the tumour being the cathode, and vice versa, and with both electrodes placed subcutaneously in the tumour vicinity. Tumour growth and the amount of electrode material in tumours were determined at different times after single-shot electrotherapy with gold needle electrodes. Different electrode configurations were employed with respect to tumours at the same current level and different current levels were used in the same electrode configuration. The amount of gold deposited in the tumour was observed with respect to tumour response to electrotherapy. Tumour growth after 0.6 rnA direct current electrotherapy was significantly retarded with respect to controls regardless of the electrode configuration, with no significant differences among them. The amount of gold per tumour, however, varied significantly with the electrode configuration. In the experiments in which both electrodes were placed subcutaneously outside the tumour, increasing current intensities produced a "dose" -dependent tumour growth response to electrotherapy which was not related to the amount of gold found in the tumours. The results obtained in this study showed that the electrode material deposition (gold) and possibly consecutive metal toxicity were not the major mechanism involved. Keywords: Tumour treatment; Direct electric current; Electrode material deposition l. Introduction Direct electric current has been reported as having antitumour activity in different tumour models [1-8] and in human clinical trials [1,9,10]. Its efficacy varied due to the different currents used (/-LA to tens of rnA) [3,11,12] duration of electrotherapy (15 min per day to continuous treatment) [13,14] and was additionally in- fluenced by different tumour models, electrode materi- als and geometry employed. In a previous study we used currents ranging from 0.1 to 1.0 rnA delivered via needle electrodes made of different metals (Pt, Pt-Ir, Au, Ag, Ti, stainless steel) in various configurations [15]. The measurements of tumour bioelectric potential * Corresponding author. 0302-4598/94/$07.00 © 1994 Elsevier Science S.A. All rights reserved SSDI 0302-4598(94)01739-N [13] temperature [15] and pH [15] did not provide satisfactory answers about the mechanisms involved. One of the physico-chemical reactions associated with direct current flow in the tissue is also metal anode dissolution. Metal anions dissolved from the positive electrode diffuse into the surrounding tissue where they can react with inorganic and organic species and potentially form toxic products [16]. In high con- centrations metals by themselves are known to have toxic properties. Also, the way in which metals were found to have an antitumour effect [17] led us to investigate the amount of electrode material deposited in a tumour after the direct current electrotherapy of tumours. In order to determine whether metal de- posited from electrodes during electrotherapy has an anti tumour effect, we sought to establish a correlation between metal deposited in tumours and antitumour effectiveness using different currents and electrode