Telomere loss in cells treated with cisplatin
Telomere loss in cells treated with cisplatin
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DOI：
10.1073/pnas.95.8.4219
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发表时间：
1998-04-14
影响因子：
11.1
通讯作者：
Lippard, SJ
中科院分区：
文献类型：
--
作者：
Ishibashi, T;Lippard, SJ
端粒在增殖细胞的永生化过程中起着重要作用。人端粒中5 '-TTAGGG-3'序列的长串联重复序列是抗癌药物顺铂的潜在靶点，其主要在DNA上形成链内d（GpG）和d（ApG）交联。目前的研究表明，顺铂处理的HeLa细胞中的端粒显着缩短和降解。杀死61%的细胞但允许一轮细胞分裂的剂量导致在诱导凋亡之前缩短的端粒。较高剂量的顺铂在第一个S期停止细胞周期进程，并引发细胞凋亡，随后端粒重复序列降解。设计了一个模型，其中细胞分裂与不完全复制和诱导细胞凋亡的顺铂可以发生解释药物诱导的端粒丢失。
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.