Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Prague.
Int J Radiat Biol. 2012 May;88(5):393-404. doi: 10.3109/09553002.2012.666001. Epub 2012 Mar 20.
Mesenchymal stem cells isolated from bone marrow (BM-MSC) and periodontal ligament (PLSC) are cells with high proliferative potential and ability to self-renewal. Characterization of these cells under genotoxic stress conditions contributes to the assessment of their prospective usage. The aim of our study was to evaluate changes in BM-MSC and PLSC caused by ionizing radiation.
Human BM-MSC and PLSC were irradiated with the doses up to 20 Gy by Co(60) and observed 13 days; viability, proliferation, apoptosis and senescence induction, and changes in expression and phosphorylation status of related proteins were studied.
Irradiation with the doses up to 20 Gy significantly reduces proliferation, but has no significant effect on cell viability. The activation of tumor suppressor protein 53 (p53) and its phosphorylations on serines 15 and 392 were detected from the first day after irradiation by 20 Gy and remained elevated to day 13. Expression of cyclin-dependent kinases inhibitor 1A (p21(Cip1/Waf1)) increased. The cell cycle was arrested in G2 phase. Instead of apoptosis we have detected hallmarks of stress-induced premature senescence: increase in cyclin-dependent kinases inhibitor 2A (p16(INK4a)) and increased activity of senescence-associated β-galactosidase.
Mesenchymal stem cells isolated from bone marrow and periodontal ligament respond to ionizing radiation by induction of stress-induced premature senescence without apparent differences in their radiation response.
骨髓间充质干细胞（BM-MSC）和牙周膜间充质干细胞（PLSC）是具有高增殖潜能和自我更新能力的细胞。在遗传毒性应激条件下对这些细胞进行特征描述有助于评估它们的预期用途。本研究的目的是评估电离辐射对 BM-MSC 和 PLSC 的影响。
用人 Co(60)对人 BM-MSC 和 PLSC 进行剂量高达 20Gy 的照射，并观察 13 天；研究了细胞活力、增殖、凋亡和衰老诱导以及相关蛋白表达和磷酸化状态的变化。
照射剂量高达 20Gy 可显著降低细胞增殖，但对细胞活力无显著影响。在 20Gy 照射后第一天即可检测到肿瘤抑制蛋白 53（p53）及其丝氨酸 15 和 392 位磷酸化的激活，并持续升高至第 13 天。细胞周期蛋白依赖性激酶抑制剂 1A（p21(Cip1/Waf1))表达增加。细胞周期被阻滞在 G2 期。我们检测到的不是凋亡，而是应激诱导的过早衰老的特征：细胞周期蛋白依赖性激酶抑制剂 2A（p16(INK4a))增加和衰老相关β-半乳糖苷酶活性增加。
骨髓和牙周膜来源的间充质干细胞对电离辐射的反应是诱导应激诱导的过早衰老，而其辐射反应没有明显差异。
