摘要
目的:研究职业性苯中毒造血损伤患者中与拓扑异构酶Ⅱα启动子调控因子c-Myb结合的组蛋白化学修饰改变,证实组蛋白乙酰化修饰水平改变在职业性苯中毒造血损伤中发挥一定的作用。方法:25例职业性苯中毒再生障碍性贫血患者为病例组,25例正常人为对照组,提取骨髓单个核细胞,用染色质免疫沉淀(Ch IP)探讨与c-Myb结合的组蛋白乙酰化和甲基化水平的改变,RT-PCR法检测c-Myb的mRNA表达水平,组蛋白去乙酰化酶(HDAC)试剂盒检测HDAC活性的变化。结果:与正常对照组相比,职业性苯中毒再生障碍性贫血患者c-Myb与乙酰化组蛋白H4、H3结合的水平下降(P<0.01),而与甲基化组蛋白H3K4和H3K9结合的水平无明显改变,差异无统计学显著性。与正常对照组相比,职业性苯中毒再生障碍性贫血患者c-Myb的mRNA表达水平降低,HDAC活性明显升高,差异均有统计学显著性(P<0.05)。结论:拓扑异构酶Ⅱα启动子调控因子c-Myb可能通过组蛋白乙酰化修饰的改变在职业性苯中毒造血损伤中发挥作用。
AIM： To investigate the role of histone modification in the changes of topoisomerase Ⅱα promoter regulatory factor c-Myb binding to histone in the occupational benzene poisoning patients with hematopoietic damnification.METHODS： The bone marrow samples were collected from 25 aplastic anemia patients caused by occupational benzene poisoning and 25 healthy controls. The binding levels of c-Myb to the histone with acetylation or methylation were detected by the technique of chromatin immunoprecipitation（ Ch IP）. The mRNA expression of c-Myb was detected by RT-PCR.The activity of histone deacetylase（ HDAC） was measured by the colorimetric HDAC assay kit. RESULTS： Compared with the controls,the binding levels of c-Myb to the acetylated histone H4 and acetylated histone H3 in the occupational benzene poisoning patients decreased（ P〈0. 01）,while those to the methylated histone H3K4 and methylated histone H3K9 didn＇t obviously change. The mRNA expression of c-Myb in the occupational benzene poisoning patients was significantly downregulated compared with the controls（ P〈0. 05）. The HDAC activity of the bone marrow mononuclear cells in the occupational benzene poisoning patients increased obviously（ P〈0. 05）. CONCLUSION： Topoisomerase Ⅱα promoter regulatory factor c-Myb may play an important role in the hematopoietic toxicities of benzene through histone acetylation modification.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2016年第5期907-911,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81172613
No.81502793)
温州市科委基金资助项目(No.Y20120004
No.Y20150034)
