Electropermeabilization in bladder cancer chemotherapy.

Abstract

Electropermeabilization has been used for the introduction of genes into cells. Using this technique, we introduced the cytotoxic drug bleomycin (BLM) into cells and examined whether the technique might be useful for the treatment of bladder cancer. For electropermeabilization in vitro, we used YTS-1 cells, a human transitional cell carcinoma line. Aliquots of cell suspension were mixed with a solution of BLM and immediately exposed to electric pulses. A high-power pulse generator was used to supply square-shaped pulses of 1250 V/cm (100 micros, eight pulses). After a 2-h post-shock incubation, cells were washed and incubated for one further hour. Then the concentration of BLM in the cells was measured using a bioassay. For electropermeabilization of tissue, we used normal male Wistar rats. The bladder was exposed and 10 mg/kg BLM was injected into the caudal vein. A series of eight pulses with a time constant of 100 micros at an electric field intensity of 1000 V/cm was applied. The bladder, liver and lungs were extracted 1 h later and prepared for quantification of the BLM concentration using the bioassay. Electrotreated cells contained significantly higher concentrations of BLM than nonelectrotreated cells. The concentration of BLM 1 h after electrotreatment in bladder tissue was 2.7 times higher than that in nonelectrotreated bladder tissue. The electropermeabilization technique has the potential to serve as a new and effective modality for the treatment of bladder cancer.