Telomere loss in cells treated with cisplatin.
Telomeres play an important role in the immortalization of proliferating cells. The long tandem repeats of 5'-TTAGGG-3' sequences in human telomeres are potential targets for the anticancer drug cisplatin, which forms mainly intrastrand d(GpG) and d(ApG) cross-links on DNA. The present study reveals that telomeres in cisplatin-treated HeLa cells are markedly shortened and degraded. A dose that killed 61% of the cells but allowed one round of cell division resulted in shortened telomeres before the induction of apoptosis. Higher doses of cisplatin halted cell cycle progression during the first S phase and triggered apoptosis followed by degradation of telomere repeats. A model in which both cell division with incomplete replication and induction of apoptosis by cisplatin could occur was devised to explain the drug-induced telomere loss.
Ishibashi
T
T
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Lippard
S J
SJ
D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003432:Cross-Linking Reagents; D004261:DNA Replication / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D016196:S Phase; D016615:Telomere / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics
D003432:Cross-Linking Reagents; D002945:Cisplatin