苯中毒骨髓单个核细胞TOPOⅡα启动子调控因子组蛋白乙酰化修饰的改变

Histone acetylation modification of topoisomerase enzyme Ⅱα promoter regulation factors in patientswith chronic benzene poisoning

目的探讨职业性苯中毒患者骨髓单个核细胞拓扑异构酶（TOP0）Ⅱα启动子调控因子组蛋白乙酰化修饰的改变。方法25例职业性苯中毒患者骨髓单个核细胞为苯中毒组，25例正常人骨髓单个核细胞为对照组，染色质免疫沉淀分析法检测TOPOⅡα启动子各调控因子组蛋白乙酰化水平的变化，反转录-聚合酶链反应（RT-PCR）法测定TOP0Ⅱα启动子各调控因子mRNA表达水平。结果（1）与对照组比较，苯中毒组rr0P0Ⅱα启动子调控因子特化蛋白l（SPl）、活化转录因子2（ATF-2）、特化蛋白3（sP3）、核因子YA（NF-YA）、抑癌基因转录因子P53、原癌基因转录因子c-MYB、ccAAT盒结合蛋白IcBP90、NF-M组蛋白H4、H3乙酰化水平下降，差异有统计学意义（P〈0．05），C-JUN组蛋白H4、H3乙酰化水平无明显改变，差异无统计学意义（P〉O．05）；（2）与正常对照组比较，苯中毒组TOP0Ⅱα启动子调控因子SPl、NF-YA、C-MYB、C-JUN及NF-MmRNA表达水平降低，差异有统计学意义（P〈O．05），ATF．2、ICBP90mRNA表达水平不变，差异无统计学意义（P〉0．05）；SP3、P53mRNA表达水平则升高，差异有统计学意义（P〈0．05）。结论（1）职业性苯中毒TOP0Ⅱα启动子调控因子组蛋白化学修饰水平的改变伴随着调控因子mRNA水平的变化；（2）TOP0Ⅱd启动子调控因子组蛋白乙酰化修饰可能在苯中毒所致的造血毒性中发挥一定的作用。

Objective To investigate histone acetylation modification of topoisomerase enzyme Ⅱα （TOPO Ⅱα promoter regulation factors in patients with chronic benzene poisoning, to explore the possible regulatory mechanism of TOPO Ⅱα involved in toxicity of chronic benzene poisoning; Methods The bone marrow samples were from 25 chronic benzene poisoning cases and 25 controls. The Chromatin Immunopreeipitation （CHIP） assay was carried out to study the possible mechanism of TOPO Ⅱα promoter regulation factors expression changes. TOPO Ⅱα 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 TOPO Ⅱα promoter regulation factors SPI, 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 TOPO Ⅱα promoter 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 historic 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.