Regular Article

British Journal of Cancer (1999) 79, 1386–1391. doi:10.1038/sj.bjc.6690222 www.bjcancer.com
Published online 26 February 1999

Increased platinum accumulation in SA-1 tumour cells after in vivo electrochemotherapy with cisplatin

M Cemaz brevear1, D Miklavc breveic breve2, J S brevec breveanc brevear3, V Dolz brevean4, R Golouh1 and G Sers brevea1

  1. 1Institute of Oncology, Zalos breveka 2, University of Ljubljana, SI-1000 Ljubljana, Slovenia
  2. 2Faculty of Electrical Engineering, University of Ljubljana, Trz breveas breveka 25, SI-1000 Ljubljana, Slovenia
  3. 3Joz breveef Stefan Institute, University of Ljubljana, Jamova 39, SI-1000 Ljubljana, Slovenia
  4. 4Medical Faculty, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia

Correspondence: G Sers brevea, Institute of Oncology, Department of Tumour Biology, Zalos breveka 2, SI-1000 Ljubljana, Slovenia

Received 12 March 1998; Revised 16 June 1998; Accepted 25 June 1998.

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Abstract

Electrochemotherapy is an anti-tumour treatment that utilizes locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. The aim of our study was to determine whether anti-tumour effectiveness of electrochemotherapy with cisplatin is a consequence of increased plasma membrane permeability caused by electroporation that enables cisplatin binding to DNA. For this purpose, anti-tumour effectiveness of electrochemotherapy was evaluated on SA-1 tumours treated with electric pulses 3 min after intravenous injection of cisplatin (4 mg kg–1). Anti-tumour effectiveness was correlated with platinum accumulation in tumours and the amount of platinum bound to DNA, as determined by atomic absorption spectrometry. In tumours treated with electrochemotherapy, cell kill was increased by a factor of 20 compared with treatment with cisplatin only, as determined from tumour growth curves. The amount of platinum bound to DNA and platinum content in the tumours treated by electrochemotherapy was approximately two times higher than in cisplatin-treated tumours. Based on our results, we conclude that in vivo application of electric pulses potentiates anti-tumour effectiveness of cisplatin by electroporation that consequently results in cisplatin increased delivery into the cells. In addition, besides electroporation, immune system and tumour blood flow changes could be involved in the observed anti-tumour effectiveness of electrochemotherapy.

Keywords:

cisplatin, platinum, electroporation, electrochemotherapy, electrothermal atomic absorption spectrometry

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