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Dose-Dependent Onset of Regenerative Program in Neutron Irradiated Mouse Skin 英文参考文献
Dose-DependentOnsetofRegenerativeProgramin
NeutronIrradiatedMouseSkin
EmilianoFratini1.,ValerioLicursi2.,MaraArtibani1,KatarzynaKobos1,PaoloColautti3 ,Rodolfo
Negri2,4,RobertoAmendola1*
1ENEA,Agenzianazionaleperlenuovetecnologie,l9energiaelosviluppoeconomicosostenibileRoma,Italy,2SapienzaUniversita` diRoma,DipartimentodiBiologiae
Biotecnologie‘‘CharlesDarwin’’,Roma,Italy,3INFN,LaboratoriNazionalidiLegnaro,Legnaro,Italy,4IstitutoPasteur-FondazioneCenciBolognetti,Roma,Italy
Abstract
Background: Tissue response to irradiation is not easily recapitulated by cell culture studies. The objective of this
investigation was to characterize, the transcriptional response and the onset of regenerative processes in mouse skin
irradiatedwithdifferentdosesoffastneutrons.
Methodology/PrincipalFindings:Tomonitorgeneralresponsetoirradiationandindividualanimaltoanimalvariation,we
performedgeneandproteinexpressionanalysiswithbothpooledandindividualmousesamples.Ahigh-throughputgene
expressionanalysis,byDNAoligonucleotidemicroarraywasdonewiththreemonthsoldC57Bl/6miceirradiatedwith0.2
and 1 Gy of mono-energetic 14 MeV neutron compared to sham irradiated controls. The results on 440 irradiation
modulatedgenes,partiallyvalidatedbyquantitativerealtimeRT-PCR,showedadose-dependentup-regulationofasub-
class of keratin and keratin associated proteins, and members of the S100 family of Ca2+-binding proteins.
Immunohistochemistry confirmed mRNA expression data enabled mapping of protein expression. Interestingly, proteins
up-regulatedinthickeningepidermis:keratin6andS100A8showedthemostsignificantup-regulationandtheleastmouse-
to-mouse variation following 0.2 Gy irradiation, in a concerted effort toward skin tissue regeneration. Conversely, mice
irradiatedat1Gyshowedmostevidenceofapoptosis(Caspase-3andTUNELstaining)andmost8-oxo-Gaccumulationat
24hpost-irradiation.Moreover,nocellproliferationaccompanied1GyexposureasshownbyKi67immunohistochemistry.
Conclusions/Significance:Thedose-depende
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