氡α粒子照射致肺支气管细胞线粒体损伤及rna表达改变-卫生毒理学专业论文.docx

氡/α粒子照射致肺支气管细胞线粒体损伤及RNA表达改变中文摘要拷贝数，线粒体膜电位和细胞内ROS水平等相关的毒性效应，以及细胞受照后发生恶性转化的情况。2、α粒子照射后，细胞周期相关的调控基因被激活而表达上调，促进细胞从G1期进入S期，从而加速了细胞周期的进程。该结果与体外氡染毒细胞的结果相同，从而证实氡对细胞的毒作用，也是通过氡及子体的衰变产物发射的α粒子所引起。3、通过高通量芯片筛选，发现了一批ρ+与ρ-细胞间以及α粒子照射前后差异表达的mRNA和miRNA。证实了部分细胞周期相关基因如CDK2和CDK4，以及部分miRNA如miR-494和let-7c在ρ+和ρ-细胞中的表达不同，提示线粒体在细胞受照射后周期进程加速和细胞恶性转化的过程中，起着至关重要的作用。关键词：线粒体；支气管上皮细胞；氡及其子体；mRNA和miRNA表达作者：聂继华指导老师：童建教授英文摘要氡/α粒子照射致肺支气管细胞线粒体损伤及RNA表达改变AlterationinMitochondriaofLung-Bronchial EpithelialCells andRNAExpressionuponExposureto Radon andAlphaParticlesAbstractObjective：Radonisthesecondleadingcauseoflungcanceraftersmoking.Healthhazardof radonand itsprogenyto lungand bronchialepithelialcellscome fromhighLETirradiationofitsalphaparticles.MitochondriaDNA（mtDNA）isoneofthemajortargetsofcarcinogens.Thisstudyistoinvestigatetheadverseeffectsofradongasand itsalphaparticlesonlungtissuesofratsaswellasonhumanbronchialepithelialcellswithknockdownofmtDNA （ρ-）,toobservealterationsinmitochondrialstructureandfunctionduringthecelltransformation,andtoscreendifferentiallyexpressed mRNA/miRNAbetweenthe?+and?-cellsuponalphairradiation,inordertoprovide experimentaldataforexploringpotentialmechanismsunderlyingmalignant transformationinducedbyradon.Methods：24healthymaleWistarratswereexposedtoradoninamulti-functionecological radonroomataconstantconcentrationtocumulativedosesof100,200and400WLM（WorkingLevel Month）.HBEcellswereexposedtoradonat20000Bq/m3for20minandrepeatedin3daystogetfirstgeneration （Rn1,andcontinuedtoobtainRn10and Rn30.）.BEAS-2Bcellswereirradiatedwithαparticlesatdosesof0.1,0.25,0.5and 1.0Gyfor2and4timesrespectively.AcellmodelwithknockdownofmtDNA（ρ-）was generatedbythetreatmentofethidiumbromide（EB）.Real-timePCR was usedtodetectchangesinmtDNAcopynumber,andthemitochondrialmembranepotential, intracellularreactiveoxygenspecies （ROS）andcellcyclewereanalyzedbyflowcytometry.Celltransformationwasreflectedbyresistancetoserum,proliferation potential,anchorageindependentgrowthinsoftagarandTranswellinvasiontest.The氡/α粒子照射