DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood 英文参考文献.docVIP

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DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood 英文参考文献.doc

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DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood 英文参考文献

DNARepairandCellCycleBiomarkersofRadiation ExposureandInflammationStressinHumanBlood HelenBudworth1.,AntoineM.Snijders1.,FrancescoMarchetti1¤,BrandonMannion1, SandhyaBhatnagar1,ElyKwoh1,YuandeTan2,ShanX.Wang3,WilliamF.Blakely4,MatthewColeman5, LeifPeterson2,AndrewJ.Wyrobek1* 1LifeSciencesDivision,LawrenceBerkeleyNationalLaboratory,Berkeley,California,UnitedStatesofAmerica,2CenterforBiostatistics,TheMethodistHospitalResearch Institute, Houston, Texas, United States of America, 3Department of Materials Science and Engineering, Department of Electrical Engineering, Stanford University, Stanford,California,UnitedStatesofAmerica,4ArmedForcesRadiobiologyResearchInstitute,UniformedServicesUniversityoftheHealthSciences,Bethesda,Maryland, UnitedStatesofAmerica,5RadiationOncology,UCDavisSchoolofMedicine,UniversityofCaliforniaDavis,Davis,California,UnitedStatesofAmerica Abstract DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expressionofDNArepair-associatedgeneswouldenhancethedetectionofindividualsexposedtoradiationversusother forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responsesofDNArepairgenesinrepeatedbloodsamplesfromhealthy,non-smokingmenandwomenexposedto2Gyof X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS). Radiation exposuresignificantlymodulatedthetranscriptexpressionof12genesof40tested(2.2E-06,p,0.03),ofwhich8showed nooverlapbetweenunirradiatedandirradiatedsamples(CDKN1A,FDXR,BBC3,PCNA,GADD45a,XPC,POLHandDDB2 ).This paneldemonstratedexcellentdoseresponsediscrimination(0.5to8Gy)inanindependenthumanbloodexvivodataset, and100%accuracyfordiscriminatingpatientswhoreceivedtotalbodyradiation.Threegenesofthispanel(CDKN1A,FDXR and BBC3) were also highly sensitive to LPS treatment in the absence of radiation exposure, and LPS co-treatment significantly affected their radiation response