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001010514 245__ $$aInter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise
001010514 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2021
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001010514 520__ $$aLarge-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples were exposed to an Iridium-192 source (1.36 TBq, Tech-Ops 880 Sentinal) at varying distances and geometries. This resulted in protracted doses ranging between 0.2 and 2.4 Gy using dose rates of 1.5-40 mGy/min and exposure times of 1 or 2.5 h. Blood samples were exposed in thermo bottles that maintained temperatures between 39 and 27.7 °C. After exposure, EDTA-blood samples were transferred into PAXGene tubes to preserve RNA. RNA was isolated in one laboratory and aliquots of four blinded RNA were sent to another five teams for dose estimation based on gene expression changes. Using an X-ray machine, samples for two calibration curves (first: constant dose rate of 8.3 mGy/min and 0.5-8 h varying exposure times; second: varying dose rates of 0.5-8.3 mGy/min and 4 h exposure time) were generated for distribution. Assays were run in each laboratory according to locally established protocols using either a microarray platform (one team) or quantitative real-time PCR (qRT-PCR, five teams). The qRT-PCR measurements were highly reproducible with coefficient of variation below 15% in ≥ 75% of measurements resulting in reported dose estimates ranging between 0 and 0.5 Gy in all samples and in all laboratories. Up to twofold reductions in RNA copy numbers per degree Celsius relative to 37 °C were observed. However, when irradiating independent samples equivalent to the blinded samples but increasing the combined exposure and incubation time to 4 h at 37 °C, expected gene expression changes corresponding to the absorbed doses were observed. Clearly, time and an optimal temperature of 37 °C must be allowed for the biological response to manifest as gene expression changes prior to running the gene expression assay. In conclusion, dose reconstructions based on gene expression measurements are highly reproducible across different techniques, protocols and laboratories. Even a radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min) can be identified. These results demonstrate the importance of the incubation conditions and time span between radiation exposure and measurements of gene expression changes when using this method in a field exercise or real emergency situation.
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001010514 7001_ $$0P:(DE-HGF)0$$aAmundson, S. A.$$b1
001010514 7001_ $$0P:(DE-HGF)0$$aBadie, C.$$b2
001010514 7001_ $$0P:(DE-HGF)0$$aBrzoska, K.$$b3
001010514 7001_ $$0P:(DE-HGF)0$$aHargitai, R.$$b4
001010514 7001_ $$0P:(DE-Juel1)133469$$aKriehuber, R.$$b5$$ufzj
001010514 7001_ $$0P:(DE-HGF)0$$aSchüle, S.$$b6
001010514 7001_ $$0P:(DE-HGF)0$$aKis, E.$$b7
001010514 7001_ $$0P:(DE-HGF)0$$aGhandhi, S. A.$$b8
001010514 7001_ $$0P:(DE-HGF)0$$aLumniczky, K.$$b9
001010514 7001_ $$0P:(DE-HGF)0$$aMorton, S. R.$$b10
001010514 7001_ $$0P:(DE-HGF)0$$aO’Brien, G.$$b11
001010514 7001_ $$0P:(DE-Juel1)133339$$aOskamp, D.$$b12$$ufzj
001010514 7001_ $$0P:(DE-HGF)0$$aOstheim, P.$$b13
001010514 7001_ $$0P:(DE-HGF)0$$aSiebenwirth, C.$$b14
001010514 7001_ $$0P:(DE-HGF)0$$aShuryak, I.$$b15
001010514 7001_ $$0P:(DE-HGF)0$$aSzatmári, T.$$b16
001010514 7001_ $$0P:(DE-HGF)0$$aUnverricht-Yeboah, M.$$b17
001010514 7001_ $$0P:(DE-HGF)0$$aAinsbury, E.$$b18
001010514 7001_ $$0P:(DE-HGF)0$$aBassinet, C.$$b19
001010514 7001_ $$0P:(DE-HGF)0$$aOestreicher, U.$$b20
001010514 7001_ $$0P:(DE-HGF)0$$aKulka, U.$$b21
001010514 7001_ $$0P:(DE-HGF)0$$aRistic, Y.$$b22
001010514 7001_ $$0P:(DE-HGF)0$$aTrompier, F.$$b23
001010514 7001_ $$0P:(DE-HGF)0$$aWojcik, A.$$b24
001010514 7001_ $$0P:(DE-HGF)0$$aWaldner, L.$$b25
001010514 7001_ $$0P:(DE-HGF)0$$aPort, M.$$b26
001010514 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-021-88403-4$$gVol. 11, no. 1, p. 9756$$n1$$p9756$$tScientific reports$$v11$$x2045-2322$$y2021
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