Bryan T M, Englezou A, Dunham M A, Reddel R R
Cancer Research Unit, Children's Medical Research Institute, Westmead, Sydney, NSW, Australia.
Exp Cell Res. 1998 Mar 15;239(2):370-8. doi: 10.1006/excr.1997.3907.
It has been proposed that the progressive shortening of telomeres in somatic cells eventually results in senescence. Previous experiments have demonstrated that many immortal cell lines have acquired telomerase activity leading to stabilization of telomere length. Telomere dynamics and telomerase activity were examined in the telomerase-positive immortal cell lines HeLa and 293 and subclones derived from them. A mass culture of HeLa cells had a stable mean telomere length over 60 population doublings (PD) in vitro. Subclones of this culture, however, had a range of mean telomere lengths indicating that telomeric heterogeneity exists within a population with a stable mean telomere length. Some of the subclones lacked detectable telomerase activity soon after isolation but regained it by PD 18, suggesting that at least some of the variation in telomere length can be attributed to variations in telomerase activity levels. 293 subclones also varied in telomere length and telomerase activity. Some telomerase-positive 293 subclones contained long telomeres that gradually shortened, demonstrating that factors other than telomerase also act to modulate telomere length. Fluctuations in telomere length in telomerase-positive immortalized cells may contribute to chromosomal instability and clonal evolution.
有人提出，体细胞中端粒的逐渐缩短最终会导致细胞衰老。先前的实验表明，许多永生细胞系已获得端粒酶活性，从而导致端粒长度稳定。对端粒酶阳性的永生细胞系HeLa和293及其衍生的亚克隆进行了端粒动力学和端粒酶活性检测。HeLa细胞的大规模培养物在体外经过60次群体倍增（PD）后，平均端粒长度保持稳定。然而，该培养物的亚克隆具有一系列平均端粒长度，这表明在平均端粒长度稳定的群体中存在端粒异质性。一些亚克隆在分离后不久缺乏可检测到的端粒酶活性，但在第18次群体倍增时恢复了活性，这表明端粒长度的至少一些变化可归因于端粒酶活性水平的变化。293亚克隆在端粒长度和端粒酶活性方面也存在差异。一些端粒酶阳性的293亚克隆含有逐渐缩短的长端粒，这表明除端粒酶外的其他因素也参与调节端粒长度。端粒酶阳性的永生化细胞中端粒长度的波动可能导致染色体不稳定和克隆进化。
