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Lookup NU author(s): Timothy Cressey, Dr Michael Tilby, Professor Herbie Newell
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Telomere stabilisation is a critical step in tumorigenesis and telomerase, an enzyme which counteracts telomeric DNA loss, is active in most tumours. Conflicting evidence has been published concerning the potential use of telomerase activity as a measurement of drug-induced tumour cell killing. In this study, the time courses of telomerase loss and induction of apoptosis were investigated in two testicular cell lines, Susa CP and 833 K, following 4-h exposure to cisplatin, melphalan or doxorubicin. Telomerase activity was only affected in both cell lines at 20 h following exposure to high concentrations of cisplatin (100× the drug concentrations causing 50% growth inhibition (IC50 values). The time course of melphalan-induced telomerase loss, which was again only apparent at 100× IC50 concentrations, varied between the cell lines and doxorubicin (100× IC50) did not induce telomerase loss in either of the cell lines. Importantly, the levels and rates of appearance of apoptotic cells (nuclear morphology and annexin V staining) were similar for all three drugs in both cell lines; i.e. cisplatin, melphalan and doxorubicin (100× IC50) caused similar frequencies of apoptosis in Susa CP cells at 24 h whereas telomerase activities were 65, 123 and 96% of the control, respectively. The possibility that telomerase activity was lost following cisplatin treatment through a direct interaction of cisplatin with telomerase was discounted. Additionally, the relative levels of the RNA component of telomerase (hTR) and mRNA for the telomerase catalytic subunit (hTERT) were not related to the observed decreases in telomerase activity. These data indicate that telomerase activity is not a reliable indicator of chemosensitivity in human testicular cancer cells. Furthermore, cisplatin-induced loss of telomerase activity is not due to a direct reaction with the enzyme or decreased hTR levels. © 2002 Elsevier Science Ltd. All rights reserved.
Author(s): Cressey, T., Tilby, M.J., Newell, D.R.
Publication type: Article
Publication status: Published
Journal: European Journal of Cancer
Year: 2002
Volume: 38
Issue: 4
Pages: 586-593
Print publication date: 01/01/2002
ISSN (print): 0959-8049
ISSN (electronic): 1879-0852
URL: http://dx.doi.org/10.1016/S0959-8049(01)00406-3
DOI: 10.1016/S0959-8049(01)00406-3
PubMed id: 11872354
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