title: Tumour-cell apoptosis after cisplatin treatment is not telomere dependent.
abstract: 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 of 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, approximately 4 kbp), HeLa 229 cells (telomere length, 20 kbp) or in the acute lymphoblastic T cell line 1301 (telomere length, approximately 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.
authors.affiliation: Henry Wellcome Biogerontology Laboratory, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
authors.forename: Jessie C
authors.initials: JC
authors.lastname: Jeyapalan
authors.forename: Gabriele
authors.initials: G
authors.lastname: Saretzki
authors.forename: Alan
authors.initials: A
authors.lastname: Leake
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Tilby
authors.forename: Thomas
authors.initials: T
authors.lastname: von Zglinicki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D015398:Signal Transduction; D016615:Telomere / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin