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Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C exposure.
J Urol. 2009 Nov; 182(5):2472-6.JU

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.

Authors+Show Affiliations

Department of Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19765756

Citation

Birare, Narendrakumar, et al. "Multidrug Resistance in a Urothelial Cancer Cell Line After 1-hour Mitomycin C Exposure." The Journal of Urology, vol. 182, no. 5, 2009, pp. 2472-6.
Birare N, Lwaleed BA, Cooper AJ. Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C exposure. J Urol. 2009;182(5):2472-6.
Birare, N., Lwaleed, B. A., & Cooper, A. J. (2009). Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C exposure. The Journal of Urology, 182(5), 2472-6. https://doi.org/10.1016/j.juro.2009.07.007
Birare N, Lwaleed BA, Cooper AJ. Multidrug Resistance in a Urothelial Cancer Cell Line After 1-hour Mitomycin C Exposure. J Urol. 2009;182(5):2472-6. PubMed PMID: 19765756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C exposure. AU - Birare,Narendrakumar, AU - Lwaleed,Bashir A, AU - Cooper,Alan J, Y1 - 2009/09/17/ PY - 2009/02/02/received PY - 2009/9/22/entrez PY - 2009/9/22/pubmed PY - 2009/10/31/medline SP - 2472 EP - 6 JF - The Journal of urology JO - J Urol VL - 182 IS - 5 N2 - 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. SN - 1527-3792 UR - https://www.unboundmedicine.com/medline/citation/19765756/Multidrug_resistance_in_a_urothelial_cancer_cell_line_after_1_hour_mitomycin_C_exposure_ L2 - https://www.jurology.com/doi/10.1016/j.juro.2009.07.007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -