Tian Xue-Lei, Lu Xue, Feng Jiang-Bin, Cai Tian-Jing, Li Shuang, Tian Mei, Liu Qing-Jie
China CDC Key Laboratory of Radiation Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing, 100088, People's Republic of China.
Radiat Environ Biophys. 2018 Aug;57(3):215-222. doi: 10.1007/s00411-018-0742-9. Epub 2018 May 17.
Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0-2 Gy Co γ-rays. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was added to modify the histone acetylation state of irradiated cells. Then, the total acetylation level, enzyme activity, dicentric plus centric rings (dic + r) frequencies, and micronucleus (MN) frequencies of the treated cells were analyzed. Results indicated that the acetylation levels of H3 and H4 significantly decreased at 1 and 24 h, respectively, after radiation exposure. The acetylation levels of H3 and H4 in irradiated groups treated with SAHA were significantly higher than those in irradiated groups that were not treated with SAHA. SAHA treatment inhibited HDAC activity in cells exposed to 0-1 Gy Co γ-rays. SAHA treatment significantly decreased dic + r/cell and MN/cell in cells exposed to 0.5 or 1.0 Gy Co γ-rays relative to that in cells that did not receive SAHA treatment. In conclusion, histone acetylation is significantly affected by IR and is involved in chromosome damage induced by Co γ-radiation.
染色体损伤与DNA损伤及错误修复有关。它可导致细胞功能障碍并最终诱发癌变。组蛋白乙酰化对于调节染色质结构和DNA损伤修复至关重要。电离辐射(IR)可改变组蛋白乙酰化。然而,响应IR暴露时组蛋白乙酰化的变化以及组蛋白乙酰化与IR诱导的染色体损伤之间的关系仍不清楚。因此,本研究调查了暴露于0 - 2 Gy Co γ射线的人淋巴细胞中H3和H4的总乙酰化水平的变化。添加了一种组蛋白脱乙酰酶(HDAC)抑制剂辛二酰苯胺异羟肟酸(SAHA)来改变受辐照细胞的组蛋白乙酰化状态。然后,分析了处理后细胞的总乙酰化水平、酶活性、双着丝粒加着丝粒环(dic + r)频率和微核(MN)频率。结果表明,辐射暴露后1小时和24小时,H3和H4的乙酰化水平分别显著降低。用SAHA处理的辐照组中H3和H4的乙酰化水平显著高于未用SAHA处理的辐照组。SAHA处理抑制了暴露于0 - 1 Gy Co γ射线的细胞中的HDAC活性。相对于未接受SAHA处理的细胞,SAHA处理显著降低了暴露于0.5或1.0 Gy Co γ射线的细胞中的dic + r/细胞和MN/细胞。总之,组蛋白乙酰化受到IR的显著影响,并参与了Co γ辐射诱导的染色体损伤。