Local Treatment of Murine Tumors by Electric Direct Current

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Abstract
Low-level direct current (0.2–1.8 mA) was demonstrated to be an antitumor agent on two different murine tumor models (fibrosarcoma Sa-1 and melanoma B-16), and has been suggested for regional cancer treatment. Its antitumor effect was achieved by introduction of single or multiple–array needle electrodes (Pt-Ir alloy) in the tumor and (an)other electrode(s) subcutaneously in its vicinity. The electrode inserted in the tumor was made anodic (anodic electrotherapy, ET) or cathodic (cathodic ET). In control groups, animals were subjected to exactly the same procedures with needle electrodes inserted at usual sites without current. In single-stimulus ET performed after the tumors have reached approximately 50 mm3 in volume with 0.2, 0.6, and 1.O mA for 30, 60, and 90 min, cathodic ET exhibited better antitumor effect than anodic ET. In both cases and at all ET durations, the antitumor effect depended proportionally on the current level applied. The antitumor effect was evaluated by following tumor growth and by microscopic estimation of the necrotization of the tumor area immediately after ET, and 24, 48, and 72 h posttreatment. Necrotization produced by cathodic ET was observed to be immediate and extensive whereas anodic ET resulted in increased necrotization only at 24 h posttreatment. In both cases the extent of necrosis was significantly higher than in control and was centrally located (site of electrode), whereas in controls it was sporadic, distributed randomly over the whole tumor area. When current was delivered via multiple–array electrode ET, the antitumor effect was slightly better in cathodic ET compared to single-electrode ET. Employing cathodic multiple-array electrode ET and using higher currents, i.e., 1.0, 1.4, and 1.8 mA in melanoma B-16, 20% and 40% cures were achieved by 1.4 and 1.8 mA single-shot ET of 1 h duration, respectively, whereas in fibrosarcoma Sa-1 no cures were accomplished. In general, different susceptibility of the two tumor models to ET was noticeable. Comparing tumor growth and necrotization after the application of direct current (0.6 mA) and alternating current (0.0 mA mean, 0.6 mA RMS), it appeared that alternating current had no impact either on necrotization of tumor tissue or on tumor growth. ET was performed on normal tissues as well. In subcutaneous tissue, thigh muscle, and liver of healthy mice immediately after 1 h of treatment using 0.6 mA in both cathodic and anodic modes, local necrotization at the site of electrode insertion was evident, with signs of acute inflammation in the vicinity. In anodic ET, vacuolization around the electrode was noticed.