Response of normal stem cells to ionizing radiation: A balance between homeostasis and genomic stability
Response of normal stem cells to ionizing radiation: A balance between homeostasis and genomic stability
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DOI：
10.1016/j.mrrev.2010.01.007
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发表时间：
2010-04-01
影响因子：
5.3
通讯作者：
Martin, Michele T.
中科院分区：
文献类型：
--
作者：
Harfouche, Ghida;Martin, Michele T.
干细胞在大多数成人组织中均有发现，它们在维持组织稳态中起着关键作用。当它们在整个生命中自我更新时，积累的遗传异常可能会损害它们的基因组完整性，并可能导致癌症。因此，干细胞（SC）可能是辐射致癌的主要目标。此外，未修复的遗传毒性损伤可能导致细胞死亡和干细胞库耗竭，损害谱系功能并加速衰老。SC生物学的发展使得能够表征干细胞对遗传毒性应激的反应及其在组织损伤中的作用。我们在这里研究这些细胞如何对电离辐射（IR）作出反应，更具体地说，它们的辐射敏感性，应激信号和DNA修复。我们首先回顾胚胎干细胞，作为一个范例的原始多能细胞，然后三个成人组织，骨髓，皮肤和肠，能够长期再生和高风险的急性辐射综合征和长期致癌。我们讨论了IR破坏组织稳态和基因组稳定性之间的平衡。我们发现，干细胞的放射敏感性并不遵循一个独特的模型，但根据组织的周转率显着不同。(C)2010 Elsevier B.V.保留所有权利。
Stem cells have been described in most adult tissues, where they play a key role in maintaining tissue homeostasis. As they self-renew throughout life, accumulating genetic anomalies can compromise their genomic integrity and potentially give rise to cancer. Stem cells (SCs) may thus be a major target of radiation carcinogenesis. In addition, unrepaired genotoxic damage may cause cell death and stem cell pool depletion, impairing lineage functionality and accelerating aging. Developments in SC biology enabled the characterization of the responses of stem cells to genotoxic stress and their role in tissue damage. We here examine how these cells react to ionizing radiation (IR), and more specifically their radiosensitivity, stress signaling and DNA repair. We first review embryonic SCs, as a paradigm of primitive pluripotent cells, then three adult tissues, bone marrow, skin and intestine, capable of long-term regeneration and at high risk for acute radiation syndromes and long-term carcinogenesis. We discuss IR disruption of the fine balance between maintenance of tissue homeostasis and genomic stability. We show that stem cell radiosensitivity does not follow a unique model, but differs notably according to the turnover rates of the tissues. (C) 2010 Elsevier B.V. All rights reserved.