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Characterisation and in vitro drug sensitivities of human transitional cell carcinoma cell lines: evaluation of their use as a model system for bladder cancer

Hepburn, Peter John; (1991) Characterisation and in vitro drug sensitivities of human transitional cell carcinoma cell lines: evaluation of their use as a model system for bladder cancer. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The concept that continuous cell lines derived from one histological type of tumour provide an in vitro model system for that disease was examined. Biological characteristics and in vitro drug sensitivities of lines derived from transitional cell carcinomas (TCC) of the human bladder are described. The isozyme phenotype, cytological appearance, cell kinetics, colony-forming efficiency, tumorigenicity and monoclonal antibody reactivities of twenty-two urothelial lines were assessed. Three types were identified; 1) fourteen distinct lines derived from different patients, 2) five cross-contaminated with one of the distinct lines (T24) and 3) three non-tumorigenic lines. Xenograft morphology and isozyme pattern were used to select representative TCC cell lines. Ten clonogenic assay procedures for measuring cytotoxicity were compared using one cell line (RT112) exposed to adriamycin and methotrexate. Significant differences between dose-response curves were obtained for the same drug indicating methods should be standardised. The relative cytotoxicities of a 24h exposure to twelve chemotherapeutic drugs against RT112 cells were compared using a clonogenic assay. Drug concentrations reducing clonogenic cell survival by 10% ranged from 2.9 ng/ml for mitoxantrone to 27.0 pg/ml for hydroxyanisole. The range and reproducibility of in vitro sensitivities to adriamycin and methotrexate were compared using eight distinct lines and four lines cross-contaminated with T24. The cross-contaminated lines had similar sensitivities, demonstrating stability during long-term culture. However there was a broads pectrum of sensitivities (>50 fold) amongst the distinct lines to methotrexate and a narrow range (<3 fold) to adriamycin. In summary, these data show that cell lines derived from human bladder tumours can retain certain biological characteristics of the tumours of origin. Taken in conjunction with published data, these results indicate that cell lines also retain the pattern of drug sensitivities of the tissue of origin, and if the differences in pharmacokinetics in vivo can be taken into account, might be used for screening new agents.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Characterisation and in vitro drug sensitivities of human transitional cell carcinoma cell lines: evaluation of their use as a model system for bladder cancer
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10123543
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