氢醌对人骨髓单个核细胞TOPOⅡα表达的影响及其可能机制

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1、氢醌对人骨髓单个核细胞TOPOⅡα表达的影响及其可能机制作者：施益芬，俞康，陈怡，任行洲，毕来喜，钱红兰【摘要】目的?：观察苯代谢物氢醌(hydroquinone，HQ)对人骨髓单个核细胞拓扑异构酶Ⅱα(TOPOⅡα)表达的影响，探讨TOPOⅡα在HQ所致造血毒性中的作用及其调控机制。方法：50μmol/LHQ培养10h的正常人骨髓单个核细胞设为实验组，等体积灭菌蒸馏水培养10h为对照组。Westernblot测定TOPOⅡα含量的变化，RT-PCR测定TOPOⅡαmRNA表达水平的改变，ChIP技术观

2、察HQ对骨髓单个核细胞TOPOⅡα启动子组蛋白乙酰化、甲基化水平的影响。结果：①与对照组相比，人骨髓单个核细胞50μmol/LHQ处理10h后，TOPOⅡα含量、TOPOⅡαmRNA水平明显下降，差异有显著性(P<0.01);②TOPOⅡα含量降低伴随着TOPOⅡα启动子组蛋白H4乙酰化、组蛋白H3K4甲基化水平的明显降低(P<0.01)、组蛋白H3K9甲基化水平升高(P?<0.05)，不伴有组蛋白H3乙酰化水平的改变(P>0.05)。结论：HQ能抑制造血细胞TOPOⅡα的表达;

3、组蛋白化学修饰可能在苯代谢物所致的造血毒性中发挥一定的作用。【关键词】氢醌类;拓扑异构酶Ⅱα;组蛋白乙酰化;组蛋白甲基化;染色质免疫沉淀分析12Abstract:?Objective:Toobservetheeffectsofhydroquinone?(HQ)?ontheexpressionoftopoisomeraseⅡα?(TOPOⅡα)?inhumanbonemarrowmononuclearcells，andtoexplorethepossibleregulatorymechanismofTOP

4、OⅡαinvolvinginthetoxicityofHQtohematopoieticcells.Methods:Humanbonemarrowmononuclearcellswasexposedto50μmol/LHQfor10h?(usedthecellswhichwereexposedtosteriledistilledwaterfor10hascontrol).TheexpressionlevelsofTOPOⅡαmRNAandproteinweredetectedwithRT-PCRtech

5、niqueandWesternblotmethod，respectively.TheChromatinImmunoprecipitation?(ChIP)?assaywascarriedouttostudythepossiblemechanismofTOPOⅡαexpres-sionchanges.Results:?TheproteinandmRNAexpressionofTOPOⅡαaftertreatedwithHQfor10hweresignificantlylowerthanthatinthec

6、ontrol?(P<0.01).ThedecreasedcontentofTOPOⅡαwasassociatedwithdescendedlevelofhistoneH4acetylation?(P<0.01)，?H3K4methylation?(P<0.01)andheightenedlevelofH3K9methylationofTOPOⅡαpromoter?(P?<0.05)?thanthatinthecontrolwiththesignificantdifference，

7、butwithoutaccompaniedwithdescentedlevelofhistoneH3acetylation?(P>0.05).Conclusion:?HQcanrepresstheexpressionofTOPOⅡαinhumanbonemarrow12mononuclearcells.Thechangesofhistonechemicalmodificationplaydefiniteimportantroleinthebenezen’shematopoietictoxicity

8、.　　Keywords:?hydroquinone;Topoisomerase?Ⅱα;histoneacetylation;histonemethylation;Chromatinimmunoprecipitation(ChIP)　　苯是明确的职业致癌物之一。苯诱发的造血系统疾病发病率高。尽管苯所致造血毒性已得到广泛重视，但其毒性机制仍未阐明。近年来，拓扑异构酶在苯致造血毒性中的作用日益受到关注[1-2]。氢醌(hydroquinone，H