Transcriptional response of BALBc mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles 英文参考文献.docVIP

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Transcriptional response of BALBc mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles 英文参考文献.doc

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Transcriptional response of BALBc mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles 英文参考文献

Rudqvistetal.EJNMMIResearch2012,2:32 /content/2/1/32 ORIGINAL RESEARCH OpenAccess TranscriptionalresponseofBALB/cmouse thyroidsfollowinginvivoastatine-211exposure revealsdistinctgeneexpressionprofiles NilsRudqvist1*,ToshimaZParris2,EmilSchüler1,KhalilHelou2andEvaForssell-Aronsson1 Abstract Background:Astatine-211(211At)isanalphaparticleemittinghalogenwithalmostoptimallinearenergytransfer forcreatingDNAdouble-strandbreaksandisthusproposedforradionuclidetherapywhenboundtotumor- seekingagents.Unbound 211Ataccumulatesinthethyroidgland,andtheconceptofbasalradiation-induced biologicaleffectsinthethyroidtissueis,toahighdegree,unknownandismostvaluable. Methods:FemaleBALB/cnudemicewereintravenouslyinjectedwith0.064to42kBqof 211At,resultingin absorbeddosesof0.05to32Gyinthethyroidgland.Thyroidswereremoved24hafterinjection;totalRNAwas extractedfrompooledthyroidsandprocessedintriplicateusingIlluminaMouseRef-8Whole-GenomeExpression Beadchips. Results:Thyroidsexposedto 211Atrevealeddistinctivegeneexpressionprofilescomparedtonon-irradiated controls.Alargernumberofgeneswereaffectedatlowabsorbeddoses(0.05and0.5Gy)comparedto intermediate(1.4Gy)andhigherabsorbeddoses(11and32Gy).Theproportionofdose-specificgenesincreased withdecreasedabsorbeddose.Additionally,1.4Gyoftenexertedoppositeregulationongeneexpression comparedtotheotherabsorbeddoses.UsingGeneOntologydata,animmunologicaleffectwasdetectedat0.05 and11Gy.Effectsoncellularresponsetoexternalstressandcellcycleregulationandproliferationweredetectedat 1.4and11Gy. Conclusions:Conclusively,thecellularresponsetoionizingradiationiscomplexanddifferswithabsorbeddose.The responseacquiredathighabsorbeddosescannotbeextrapolateddowntolowabsorbeddosesorviceversa.Wealso demonstratedthatthethyroid-alreadyatabsorbeddosessimilartothoseobtainedinradionuclidetherapy-responds withexpressionofahighnumberofgenes.Duetotheincreasedheterogeneousirradiationatlowabsorbeddoses,we suggestthatthisresponsepartlyoriginatesfromnon-irradiatedcellsinthet