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Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C exposure

Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C exposure
Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C exposure
Purpose: a factor pertinent to the design of cancer chemotherapy is multidrug resistance. Research in this area conventionally involves in vitro models using resistant cell lines generated by continuous low dose drug exposure for many months, unlike the exposure experienced by residual superficial bladder cancer cells during chemotherapy adjuvant to resection. Recently we noted a measure of multidrug resistance induced by 3 short exposures to mitomycin C during 10 weeks. We currently report detectable functional resistance after a single 1-hour insult.
Materials and methods: RT112 bladder cancer cells (Catalog No. ACC 418, Deutsche Sammlung von Mikroorganismen und Zellkulturen, Braunschweig, Germany) were exposed to a range of mitomycin C concentrations for 1 hour. Cells regrew in 3 of 24 cultures at 15.6, 3.91 and 0.98 mg/ml exposure. These cells were subjected to 3 functional tests of cross resistance to epirubicin, including MTT cytotoxicity assay, quantitative accumulation by flow cytometry and nuclear uptake or exclusion by live cell fluorescence microscopy.
Results: MTT assay and flow cytometry revealed clear indications of resistance. Intracellular distribution, in which nuclear exclusion indicates resistance, was distinctively resistant in 1 subline and another 2 were equivocal.
Conclusions: results indicate that some multidrug resistance potential exists even in a cloned cell line that is capable of surviving 1 short drug exposure and expanding after that insult. The exposures used are consistent with those probably experienced by many superficial transitional cell carcinoma cells during an intravesical chemotherapy application. The result gives added weight to considering multidrug resistance induction in dose scheduling or drug combinations for topical chemotherapy
urinary bladder, urothelium, carcinoma, transitional cell, mitomycin, drug resistance, multiple
0022-5347
2472-2476
Birare, Narendrakumar
f8c77520-9ef5-4f40-a5af-34927809612e
Lwaleed, Bashir A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Cooper, Alan J.
65dcd1e1-3fcd-46b8-ad5f-f17e0d5b80a5
Birare, Narendrakumar
f8c77520-9ef5-4f40-a5af-34927809612e
Lwaleed, Bashir A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Cooper, Alan J.
65dcd1e1-3fcd-46b8-ad5f-f17e0d5b80a5

Birare, Narendrakumar, Lwaleed, Bashir A. and Cooper, Alan J. (2009) Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C exposure. The Journal of Urology, 182 (5), 2472-2476. (doi:10.1016/j.juro.2009.07.007).

Record type: Article

Abstract

Purpose: a factor pertinent to the design of cancer chemotherapy is multidrug resistance. Research in this area conventionally involves in vitro models using resistant cell lines generated by continuous low dose drug exposure for many months, unlike the exposure experienced by residual superficial bladder cancer cells during chemotherapy adjuvant to resection. Recently we noted a measure of multidrug resistance induced by 3 short exposures to mitomycin C during 10 weeks. We currently report detectable functional resistance after a single 1-hour insult.
Materials and methods: RT112 bladder cancer cells (Catalog No. ACC 418, Deutsche Sammlung von Mikroorganismen und Zellkulturen, Braunschweig, Germany) were exposed to a range of mitomycin C concentrations for 1 hour. Cells regrew in 3 of 24 cultures at 15.6, 3.91 and 0.98 mg/ml exposure. These cells were subjected to 3 functional tests of cross resistance to epirubicin, including MTT cytotoxicity assay, quantitative accumulation by flow cytometry and nuclear uptake or exclusion by live cell fluorescence microscopy.
Results: MTT assay and flow cytometry revealed clear indications of resistance. Intracellular distribution, in which nuclear exclusion indicates resistance, was distinctively resistant in 1 subline and another 2 were equivocal.
Conclusions: results indicate that some multidrug resistance potential exists even in a cloned cell line that is capable of surviving 1 short drug exposure and expanding after that insult. The exposures used are consistent with those probably experienced by many superficial transitional cell carcinoma cells during an intravesical chemotherapy application. The result gives added weight to considering multidrug resistance induction in dose scheduling or drug combinations for topical chemotherapy

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More information

Published date: November 2009
Keywords: urinary bladder, urothelium, carcinoma, transitional cell, mitomycin, drug resistance, multiple

Identifiers

Local EPrints ID: 73056
URI: https://eprints.soton.ac.uk/id/eprint/73056
ISSN: 0022-5347
PURE UUID: 380a35c7-8175-43cb-8832-69f8416a863b

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Date deposited: 02 Mar 2010
Last modified: 19 Jul 2019 23:41

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