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

Electrochemotherapy is an anti-tumour treatment that utilizes locally deliv ered electric pulses to increase cytotoxicity of chemotherapeutic drugs. Th e aim of our study was to determine whether anti-tumour effectiveness of el ectrochemotherapy with cisplatin is a consequence of increased plasma membr ane permeability caused by electroporation that enables cisplatin binding t o DNA. For this purpose, anti-tumour effectiveness of electrochemotherapy w as evaluated on SA-1 tumours treated with electric pulses 3 min after intra venous 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 gro wth 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 i n vivo application of electric pulses potentiates anti-tumour effectiveness of cisplatin by electroporation that consequently results in cisplatin inc reased delivery into the cells. In addition, besides electroporation, immun e system and tumour blood flow changes could be involved in the observed an ti-tumour effectiveness of electrochemotherapy.