Objective: The aim of this study was to examine the usefulness of an electropermeabilization method in the administration of a chemotherapeutic agent in bladder cancer in the rat. Materials and Methods: N-Butyl-N-(4-hydroxybutyl)-nitrosamine was used to induce bladder tumors in Wistar rats. Rats in group 1 were given a sham treatment. Rats in group 2 received an injection of bleomycin (BLM). Rats in group 3 received a series of eight 100-µs square-wave pulses at an electric field intensity of 1,000 V/cm (electropermeabilization) applied to the bladder. Rats in group 4 were treated with square-wave pulses after the injection of BLM. Nine days after the various treatments, all the bladders were removed and examined histopathologically. Results: Histopathological examination revealed severe damage to tumors in group 4 exclusively. Conclusion: The cytotoxic effect of BLM on bladder cancer tissue was enhanced by electropermeabilization.

1.
Orlowski S, Mie LM: Cell electropermeabilization: A new tool for biochemical and pharmacological studies. Biochim Biophys Acta 1993;1154:51–63.
2.
Escande-Geraud ML, Rols MP, Dupont MA, Gas N, Teissie J: Reversible plasma membrane ultrastructural changes correlated with electropermeabilization in Chinese hamster ovary cells. Biochim Biophys Acta 1998;939:247–259.
3.
Hibino M, Itoh H, Kinosita K Jr: Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. Biophys J 1993;64:1789–1800.
4.
Orlowski S, Belehradek J Jr, Paoletti C, Mir LM: Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. Biochem Pharmacol 1988;37:4723–4733.
5.
Kubicka P, Kramaric G: Electroporation of cosmid DNA into bacterial cells. Trends Genet 1994;10:5.
6.
Teissie J, Rols MP: An experimental evaluation of the critical potential difference inducing cell membrane electropermeabilization. Biophys J 1993;65:409–413.
7.
Kubota Y, Nakada T, Yanai H, Kakizaki H, Sasagawa I, Watanabe M: Electropermeabilization in bladder cancer chemotherapy. Cancer Chemother Pharmacol 1996;39:67–70.
8.
Tam JE, Davis CH, Wyrick PB: Expression of recombinant DNA introduced into Chlamydia trachomatis by electroporation. Can J Microbiol 1994;40:583–591.
9.
Mir LM, Banoun H, Paoletti C: Introduction of definite amounts of non-permeant molecules into living cells after electropermeabilization: Direct access to cytosol. Exp Cell Res 1988;175:15–25.
10.
Jastroboff MM, Sokoloski JA, Bertino JR, Narayanann R: Use of electroporation to study the cytotoxic effects of fluorodeoxyuridylate in intact cells. Biochem Pharmacol 1987;36:1345–1348.
11.
Milvik JE, Pettersen EO, Gordon PB, Siglen PO: Increase in cis dichlorodiammineplatinum (II) cytotoxicity upon reversible electropermeabilization of the plasma membrane in cultured human NHIK 3025 cells. Eur J Cancer Clin Oncol 1986;22:1523–1530.
12.
Poddevin B, Orlowski S, Belehradek J Jr, Mir LM: Very high cytotoxicity of bleomycin introduced into the cytosol of cells in culture. Biochem Pharmacol 1991;42(suppl):67–75.
13.
Belehradek M, Domenge C, Luboinski B, Orlowski S, Belehradek J Jr, Mir LM: Electrochemotherapy, a new antitumor treatment, first clinical phase I-II trial. Cancer 1993;72:3694–3700.
14.
Domenge C, Orlowski S, Luboinski B, De Baere T, Schwaab G, Belehradek J Jr, Mir LM: Antitumor electrochemotherapy. New advances in the clinical protocol. Cancer 1996;77:956–963.
15.
Salford LG, Persson BRR, Brun A, Ceberg CP, Kongstad PC, Mir LM: A new brain tumour therapy combining bleomycin with in vivo electropermeabilization. Biochem Biophys Res Comm 1993;194:938–943.
16.
Henry K, Miller J, Mori M, Loening S, Fallon B: Comparison of transurethral resection to radical therapies for stage B bladder tumors. J Urol 1988;140:964–967.
17.
Prout GR Jr, Shipley WU, Kufman DS, Heney NM, Griffin PP, Althausen AF, Bassil B, Nocks BN, Parkhurst EC, Young JJ II: Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy. J Urol 1990;144:1128–1136.
18.
Russell KJ, Boileau MA, Higano C, Collins C, Russell AH, Koh W, Cole SB, Chapaman WH, Griffin TW: Combined 5-fluorouracil and irradiation for transitional cell carcinoma of the urinary bladder. Int J Radiat Oncol Biol Phys 1990;19:693–699.
19.
Bracken RB, Johnson DE, Rodriquez L, Samuels ML, Ayala A: Treatment of multiple superficial tumor of bladder with intravesical bleomycin. Urology 1977;9:161–163.
20.
Habs M, Ang J, Schmahl D: Chemotherapy studies in autochthonous rat tumors. Z Krebsforsch 1977;89:119–136.
21.
Tounekti O, Pron G, Belehradek J Jr, Mir LM: Bleomycin, an apoptosis-mimetic drug that induces two types of cell death depending on the number of molecules internalized. Cancer Res 1993;53:5462–5469.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.