Factors influencing the sensitivity of two human bladder carcinoma cell lines to cis-diamminedichloroplatinum(II) |
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| Authors: | P Bedford M C Walker H L Sharma A Perera C A McAuliffe J R Masters B T Hill |
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| Affiliation: | 1. Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund Laboratories, Lincoln''s Inn Fields, London, WC2A 3PX U.K.;2. Department of Histopathology, Institute of Urology, St. Paul''s Hospital, 24 Endell Street, London, WC2H 9AE U.K.;3. The Manchester Platinum Group, Department of Medical Biophysics, University of Manchester Medical School, Manchester, M13 9PT U.K.;4. Department of Inorganic Chemistry, University of Manchester Institute of Science and Technology, Manchester, M60 1QD U.K.;1. School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;2. Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;1. Tiradentes University, Av. Murilo Dantas 300, 49032-490, Aracaju, SE, Brazil;2. Institute of Technology and Research, Av. Murilo Dantas 300, 49032-490, Aracaju, SE, Brazil;3. School of Technology, Pontifical Catholic University of Rio Grande do Sul - PUCRS, Av. Ipiranga 6681, 90619-900, Porto Alegre, RS, Brazil;4. School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul - PUCRS, Av. Ipiranga 6681, 90619-900, Porto Alegre, RS, Brazil;1. Institute of Molecular Medicine I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany;2. Department of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany |
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| Abstract: | A two-fold difference in sensitivity to cis-diamminedichloroplatinum(II) (cisplatin), as judged by colony forming assays, has been demonstrated in two human bladder carcinoma continuous cell lines. Approximately twice as many DNA-DNA interstrand cross-links (ISL) and a 2-fold greater inhibition of DNA synthesis occurred in the more sensitive T24 cell line than in the RT112 cell line after exposure to the same concentrations of cisplatin. Equitoxic concentrations of cisplatin resulted in similar extents of ISL and inhibition of DNA synthesis in both cell lines. Although drug uptake was identical, twice as much cisplatin was bound to the DNA of T24 cells than RT112 cells. However after equitoxic concentrations of cisplatin the DNA from both cell lines was platinated to a similar extent. In addition, levels of glutathione (GSH), glutathione reductase (GR) and total glutathione-S-transferases (GST) were higher in the less sensitive RT112 cell line. |
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