Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 118, Issue 11, Pages 2727-2734Publisher
WILEY
DOI: 10.1002/ijc.21675
Keywords
telomeres; telomerase; cisplatin; neuroblastoma; apoptosis; DNA damage
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Cisplatin is a major chemotherapeutic agent, especially for the treatment of neuroblastoma. Telomeres with their sequence (TTAGGG)(n) are probable targets for cisplatin intrastrand cross-linking, but the role or telomeres in mediating cisplatin cytotoxicity is not clear. After exposure to cisplatin as single dose or continuous treatment, we found no loss of telomeres in either SHSY5Y neuroblastoma cells (telomere length, similar to 4 kbp), HeLa 229 cells (telomere length, 20 kbp) or in the acute lymphoblastic T cell line 1301 (telomere length, similar to 80 kbp). There was no induction of telomeric single strand breaks, telomeric overhangs were not degraded and telomerase activity was down-regulated only after massive onset of apoptosis. In contrast, cisplatin induced a delayed formation of DNA strand breaks and induced DNA damage foci containing gamma-H2A.X at nontelomeric sites. Interstitial DNA damage appears to be more important than telomere loss or telomeric damage as inducer of the signal pathway towards apoptosis and/or growth arrest in cisplatin-treated tumour cells. (c) 2005 Wiley-Liss, Inc.
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