Heterogeneity in premature senescence by oxidative stress correlates with differential DNA damage during the cell cycle
Heterogeneity in premature senescence by oxidative stress correlates with differential DNA damage during the cell cycle
复制标题
DOI：
10.1016/j.dnarep.2005.06.003
复制
发表时间：
2005-09-28
期刊：
影响因子：
3.8
通讯作者：
Hales, CN
中科院分区：
文献类型：
--
作者：
Chen, JH;Ozanne, SE;Hales, CN
在培养的原代人成纤维细胞中，通过复制和氧化应激引起的细胞衰老的发展是不均匀的。为了研究这是否是由于在细胞周期的不同阶段的DNA的易感性的异质性，我们进行同步化的细胞氧化应激，并检查DNA损伤的程度和其对细胞衰老的诱导的长期影响。在这里，我们首先显示了显着的异质性，DNA损伤检测标记的氧化应激引起的双链断裂在异步人成纤维细胞培养。细胞周期同步化后的氧化应激表明，DNA在S期是最容易受到氧化应激，而DNA在静止期是最具抵抗力的。DNA修复是一个持续的过程后，感知DNA损伤;可修复的DNA损伤修复，即使在细胞中含有持续的DNA损伤。持续性DNA损伤的程度与DNA复制和SA-P-gal活性的永久停止密切相关。处于S期的细胞所遇到的氧化应激导致更持久的DNA损伤，更持久的细胞周期停滞和诱导早衰。(c)2005 Elsevier B. V.保留所有权利。
The development of cellular senescence both by replication and by oxidative stress is not homogenous in cultured primary human fibroblasts. To investigate whether this is due to the heterogeneity in the susceptibility of DNA in different phases of the cell cycle, we subjected synchronised cells to oxidative stress and examined the extent of DNA damage and its long-term effects on the induction of cellular senescence. Here, we first show marked heterogeneity in DNA damage as detected by markers of double strand breaks caused by oxidative stress in an asynchronous human fibroblast culture. Cell cycle synchronization followed by oxidative stress demonstrated that DNA in S-phase is most susceptible to oxidative stress whereas DNA in the quiescent phase is most resistant. DNA repair is an ongoing process after sensing DNA damage; reparable DNA damage is repaired even in cells that contain persistent DNA damage. The extent of persistent DNA damage is tightly correlated with permanent cessation of DNA replication and SA-P-gal activity. Oxidative stress encountered by cells in S-phase resulted in more persistent DNA damage, more permanent cell cycle arrest and the induction of premature senescence. (c) 2005 Elsevier B.V. All rights reserved.