Effects of electropermeabilization after the administration of anticancer drugs on transitional cell carcinoma.
OBJECTIVE
To assess in vitro and in vivo the potential utility of electropermeabilization (EP) as an anticancer drug delivery system for the treatment of transitional cell carcinoma (TCC).


METHODS
To analyse the effects of EP on the internalization of adriamycin and bleomycin by cells, aliquots of a suspension of YTS-1 carcinoma cells (derived from a human TCC line) were mixed with a solution of adriamycin or bleomycin and then exposed immediately to an electric field (1000 V/cm, 1 Hz, 100-micros square wave, eight pulses). After a 2-h incubation the concentration of each drug in the cells was measured by high-performance liquid chromatography (for adriamycin) and by bioassay (for bleomycin). The concentrations of drugs in the cells were compared with untreated cells. To analyse the effects of EP on cytotoxicity, the same treatments were applied to a suspension of cells plus adriamycin or bleomycin and then the cells incubated for 6 h with tritiated thymidine ([3H]-TdR), monitoring the incorporation of [3H]-TdR into the cells. Cells with no electrotreatment acted as controls. To assess the effects on tumours in vivo, YTS-1 cells were transplanted subcutaneously into nude mice; when the tumours had reached 7 mm in diameter, EP was applied (using electrical pulses as before, 10 min after the direct injection of bleomycin into the tumour). Tumours were then measured regularly and compared with sham-treated tumours, tumours treated with electric pulses alone, and tumours treated with bleomycin alone. Survival was also compared.


RESULTS
There were no significant differences in the levels of adriamycin between cells with and with no EP, whereas there was a marked difference for bleomycin. Growth inhibition by adriamycin with and with no EP was similar, while the growth-inhibitory effects of bleomycin were almost doubled. There was a reduction in tumour size only in the group treated with bleomycin plus electric pulses and two of five tumours disappeared completely. Survival in this group was also significantly better than in the other groups.


CONCLUSIONS
EP after administering bleomycin might be an effective treatment for TCC.
Yanai
H
H
Department of Urology, Yamagata University School of Medicine, Yamagata, Japan.
Kubota
Y
Y
Nakada
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004357:Drug Synergism; D004560:Electricity; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010539:Permeability; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D001761:Bleomycin; D004317:Doxorubicin