Chromatin remodeling modulates radiosensitivity of the daughter cells derived from cell population exposed to low- and high-LET irradiation.
Chromatin remodeling modulates radiosensitivity of the daughter cells derived from cell population exposed to low- and high-LET irradiation.
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染色质重塑调节来自暴露于低和高 LET 辐射的细胞群的子细胞的放射敏感性
DOI：
10.18632/oncotarget.17275
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发表时间：
2017-08-08
期刊：
影响因子：
--
通讯作者：
Shao C
中科院分区：
文献类型：
--
作者：
Wang P;Yuan D;Guo F;Chen X;Zhu L;Zhang H;Wang C;Shao C
辐射效应依赖于线性能量转移(LET)，但辐射群体来源的子代细胞(DC)是否具有辐射抗性尚不清楚，更不用说其潜在的机制了。通过对细胞存活率、增殖和γH_2AX灶的检测，本研究发现γ-射线照射细胞来源的DC(DC-γ)比未照射的亲本对照细胞(DC-α-α)对辐射的抵抗力增强，但其辐射敏感性没有改变。经等剂量γ射线和α粒子照射后，DC-γ的组蛋白H3赖氨酸9二甲基化(H3K9me3)焦点数和组蛋白脱乙酰基酶活性明显高于DC-α及其亲本对照，表明DC-γ中形成了较高水平的异染色质，而DC-α中未见。用HDAC抑制剂SAHA处理细胞，通过抑制H3K9M3和HP-1a蛋白的表达，并触发乙酰化核心组蛋白H3(Ac-H3)的表达，降低了异染色质结构域的水平。经SAHA处理后，DCs-γ的辐射抗性表型被消除，DCs-γ、DCs-α及其亲本细胞的辐射敏感性接近同一水平。我们目前的结果显示，γ射线而不是α粒子可以诱导DC发生染色质重塑和异染色质异染色化，从而导致DC发生辐射抵抗，提示联合应用照射和HDAC抑制剂可以作为一种潜在的肿瘤治疗策略，特别是对于低LET照射的分割放射治疗。
Radiation effects are dependent of linear energy transfer (LET), but it is still obscure whether the daughter cells (DCs) derived from irradiated population are radioresistance and much less the underlying mechanism. With the measurements of survival, proliferation and γH2AX foci, this study shows that the DCs from γ-ray irradiated cells (DCs-γ) became more radioresistant than its parent control without irradiation, but the radiosensitivity of DCs from α-particle irradiated cells (DCs-α) was not altered. After irradiation with equivalent doses of γ-rays and α-particles, the foci number of histone H3 lysine 9 dimethylation (H3K9me3) and the activity of histone deacetylase (HDAC) in DCs-γ was extensively higher than these in DCs-α and its parent control, indicating that a higher level of heterochromatin was formed in DCs-γ but not in DCs-α. Treatment of cells with SAHA (an inhibitor of HDAC) decreased the level of heterochromatin domains by inhibiting the expressions of H3K9m3 and HP-1a proteins and triggering the expression of acetylated core histone H3 (Ac-H3). When cells were treated with SAHA, the radioresistance phenotype of DCs-γ was eliminated so that the radiosensitivities of DCs-γ, DCs-α and their parent cells approached to same levels. Our current results reveal that γ-rays but not α-particles could induce chromatin remodeling and heterochromatinization which results in the occurrence of radioresistance of DCs, indicating that the combination treatment of irradiation and HDAC inhibitor could serve as a potential cancer therapy strategy, especially for the fraction radiotherapy of low-LET irradiation.
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DOI：
10.1016/j.mrfmmm.2010.12.003
发表时间：
2011-02-10
影响因子：
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