000811945 001__ 811945
000811945 005__ 20210129223950.0
000811945 0247_ $$2doi$$a10.1667/RR14221.1
000811945 0247_ $$2ISSN$$a0033-7587
000811945 0247_ $$2ISSN$$a1938-5404
000811945 0247_ $$2WOS$$aWOS:000370734200002
000811945 037__ $$aFZJ-2016-04255
000811945 082__ $$a610
000811945 1001_ $$0P:(DE-HGF)0$$aAbend, M.$$b0$$eCorresponding author
000811945 245__ $$aExamining Radiation-Induced In Vivo and In Vitro Gene Expression Changes of the Peripheral Blood in Different Laboratories for Biodosimetry Purposes: First RENEB Gene Expression Study
000811945 260__ $$aGreat Falls, Va.$$bRadiation Research Society$$c2016
000811945 3367_ $$2DRIVER$$aarticle
000811945 3367_ $$2DataCite$$aOutput Types/Journal article
000811945 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1506327211_17745
000811945 3367_ $$2BibTeX$$aARTICLE
000811945 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000811945 3367_ $$00$$2EndNote$$aJournal Article
000811945 520__ $$aThe risk of a large-scale event leading to acute radiation exposure necessitates the development of high-throughput methods for providing rapid individual dose estimates. Our work addresses three goals, which align with the directive of the European Union's Realizing the European Network of Biodosimetry project (EU-RENB): 1. To examine the suitability of different gene expression platforms for biodosimetry purposes; 2. To perform this examination using blood samples collected from prostate cancer patients (in vivo) and from healthy donors (in vitro); and 3. To compare radiation-induced gene expression changes of the in vivo with in vitro blood samples. For the in vitro part of this study, EDTA-treated whole blood was irradiated immediately after venipuncture using single X-ray doses (1 Gy/min(-1) dose rate, 100 keV). Blood samples used to generate calibration curves as well as 10 coded (blinded) samples (0-4 Gy dose range) were incubated for 24 h in vitro, lysed and shipped on wet ice. For the in vivo part of the study PAXgene tubes were used and peripheral blood (2.5 ml) was collected from prostate cancer patients before and 24 h after the first fractionated 2 Gy dose of localized radiotherapy to the pelvis [linear accelerator (LINAC), 580 MU/min, exposure 1-1.5 min]. Assays were run in each laboratory according to locally established protocols using either microarray platforms (2 laboratories) or qRT-PCR (2 laboratories). Report times on dose estimates were documented. The mean absolute difference of estimated doses relative to the true doses (Gy) were calculated. Doses were also merged into binary categories reflecting aspects of clinical/diagnostic relevance. For the in vitro part of the study, the earliest report time on dose estimates was 7 h for qRT-PCR and 35 h for microarrays. Methodological variance of gene expression measurements (CV ≤10% for technical replicates) and interindividual variance (≤twofold for all genes) were low. Dose estimates based on one gene, ferredoxin reductase (FDXR), using qRT-PCR were as precise as dose estimates based on multiple genes using microarrays, but the precision decreased at doses ≥2 Gy. Binary dose categories comprising, for example, unexposed compared with exposed samples, could be completely discriminated with most of our methods. Exposed prostate cancer blood samples (n = 4) could be completely discriminated from unexposed blood samples (n = 4, P < 0.03, two-sided Fisher's exact test) without individual controls. This could be performed by introducing an in vitro-to-in vivo correction factor of FDXR, which varied among the laboratories. After that the in vitro-constructed calibration curves could be used for dose estimation of the in vivo exposed prostate cancer blood samples within an accuracy window of ±0.5 Gy in both contributing qRT-PCR laboratories. In conclusion, early and precise dose estimates can be performed, in particular at doses ≤2 Gy in vitro. Blood samples of prostate cancer patients exposed to 0.09-0.017 Gy could be completely discriminated from pre-exposure blood samples with the doses successfully estimated using adjusted in vitro-constructed calibration curves.
000811945 536__ $$0G:(DE-HGF)POF3-899$$a899 - ohne Topic (POF3-899)$$cPOF3-899$$fPOF III$$x0
000811945 588__ $$aDataset connected to CrossRef
000811945 7001_ $$0P:(DE-HGF)0$$aBadie, C.$$b1
000811945 7001_ $$0P:(DE-HGF)0$$aQuintens, R.$$b2
000811945 7001_ $$0P:(DE-Juel1)133469$$aKriehuber, R.$$b3$$ufzj
000811945 7001_ $$0P:(DE-HGF)0$$aManning, G.$$b4
000811945 7001_ $$0P:(DE-HGF)0$$aMacaeva, E.$$b5
000811945 7001_ $$0P:(DE-HGF)0$$aNjima, M.$$b6
000811945 7001_ $$0P:(DE-Juel1)133339$$aOskamp, D.$$b7$$ufzj
000811945 7001_ $$0P:(DE-HGF)0$$aStrunz, S.$$b8
000811945 7001_ $$0P:(DE-HGF)0$$aMoertl, S.$$b9
000811945 7001_ $$0P:(DE-HGF)0$$aDoucha-Senf, S.$$b10
000811945 7001_ $$0P:(DE-HGF)0$$aDahlke, S.$$b11
000811945 7001_ $$0P:(DE-HGF)0$$aMenzel, J.$$b12
000811945 7001_ $$0P:(DE-HGF)0$$aPort, M.$$b13
000811945 773__ $$0PERI:(DE-600)2135113-2$$a10.1667/RR14221.1$$gVol. 185, no. 2, p. 109 - 123$$n2$$p109 - 123$$tRadiation research$$v185$$x1938-5404$$y2016
000811945 909CO $$ooai:juser.fz-juelich.de:811945$$pVDB
000811945 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)133469$$aForschungszentrum Jülich$$b3$$kFZJ
000811945 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)133339$$aForschungszentrum Jülich$$b7$$kFZJ
000811945 9131_ $$0G:(DE-HGF)POF3-899$$1G:(DE-HGF)POF3-890$$2G:(DE-HGF)POF3-800$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0
000811945 9141_ $$y2017
000811945 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000811945 915__ $$0StatID:(DE-HGF)0430$$2StatID$$aNational-Konsortium
000811945 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000811945 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000811945 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bRADIAT RES : 2014
000811945 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000811945 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000811945 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000811945 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000811945 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000811945 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000811945 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000811945 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000811945 920__ $$lyes
000811945 9201_ $$0I:(DE-Juel1)S-US-20090406$$kS-US$$lSicherheit und Strahlenschutz, Umgebungsüberwachung,Strahlenbiologie$$x0
000811945 980__ $$ajournal
000811945 980__ $$aVDB
000811945 980__ $$aI:(DE-Juel1)S-US-20090406
000811945 980__ $$aUNRESTRICTED