[慢性苯中毒患者拓扑异构酶Ⅱα启动子调控因子的组蛋白乙酰化修饰]
[Histone acetylation modification of topoisomerase enzyme Ⅱα promoter regulation factors in patients with chronic benzene poisoning].
作者信息
Shi Yifen, Qian Shanhu, Li Jiaqi, Yu Kang
机构信息
Department of Hematology, the first affiliated hospital of Wenzhou Medical University, Wenzhou 325000, China.
出版信息
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2016 Jan;34(1):8-12. doi: 10.3760/cma.j.issn.1001-9391.2016.01.002.
OBJECTIVE
To investigate histone acetylation modification of topoisomerase enzyme Ⅱα (TOPOⅡα) promoter regulation factors in patients with chronic benzene poisoning, to explore the possible regulatory mechanism of TOPOⅡα involved in toxicity of chronic benzene poisoning;
METHODS
The bone marrow samples were from 25 chronic benzene poisoning cases and 25 controls. The Chromatin Immunoprecipitation (ChIP) assay was carried out to study the possible mechanism of TOPOⅡα promoter regulation factors expression changes. TOPOⅡα promoter regulation factors mRNA were detected by RT-PCR technique.
RESULTS
(1) Compared with the control, the histone H4 acetylation, histone H3 acetylation level of TOPOⅡα promoter regulation factors SP1, ATF-2, SP3, NF-YA, P53, C-MYB, ICBP90, NF-M in chronic benzene poisoning patients decreased, with the significant difference (P<0.05) , except for C-JUN (P>0.05) ; (2) The mRNA expression of TOPOⅡαpromoter regulation factors SP1, NF-YA, C-MYB, C-JUN and NF-M were significantly lower than in the control with the significant difference (P<0.05) , while the expression of SP3、P53 mRNA increased (P<0.05) , ATF-2、ICBP90 mRNA wasn't changed (P>0.05) .
CONCLUSION
(1) Chronic benzene poisoning TOPO Ⅱα promoter regulation factors histone modification changes accompanied with mRNA level changed. (2) Histone acetylation modification of topoisomerase enzyme Ⅱα promoter regulation factors takes important role in the benezen's Hematopoietic toxicity.
目的
探讨慢性苯中毒患者拓扑异构酶Ⅱα（TOPOⅡα）启动子调控因子的组蛋白乙酰化修饰情况，以探索TOPOⅡα参与慢性苯中毒毒性作用的可能调控机制。
方法
选取25例慢性苯中毒患者及25例对照者的骨髓样本。采用染色质免疫沉淀（ChIP）试验研究TOPOⅡα启动子调控因子表达变化的可能机制。运用RT-PCR技术检测TOPOⅡα启动子调控因子mRNA。
结果
（1）与对照组相比，慢性苯中毒患者中TOPOⅡα启动子调控因子SP1、ATF-2、SP3、NF-YA、P53、C-MYB、ICBP90、NF-M的组蛋白H4乙酰化、组蛋白H3乙酰化水平降低，差异有统计学意义（P<0.05），C-JUN除外（P>0.05）；（2）TOPOⅡα启动子调控因子SP1、NF-YA、C-MYB、C-JUN和NF-M的mRNA表达明显低于对照组，差异有统计学意义（P<0.05），而SP3、P53 mRNA表达升高（P<0.05），ATF-2、ICBP90 mRNA表达无变化（P>0.05）。
结论
（1）慢性苯中毒时TOPOⅡα启动子调控因子的组蛋白修饰变化伴随mRNA水平改变。（2）拓扑异构酶Ⅱα启动子调控因子的组蛋白乙酰化修饰在苯的造血毒性中起重要作用。
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