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@ARTICLE{Abend:1010514,
      author       = {Abend, M. and Amundson, S. A. and Badie, C. and Brzoska, K.
                      and Hargitai, R. and Kriehuber, R. and Schüle, S. and Kis,
                      E. and Ghandhi, S. A. and Lumniczky, K. and Morton, S. R.
                      and O’Brien, G. and Oskamp, D. and Ostheim, P. and
                      Siebenwirth, C. and Shuryak, I. and Szatmári, T. and
                      Unverricht-Yeboah, M. and Ainsbury, E. and Bassinet, C. and
                      Oestreicher, U. and Kulka, U. and Ristic, Y. and Trompier,
                      F. and Wojcik, A. and Waldner, L. and Port, M.},
      title        = {{I}nter-laboratory comparison of gene expression
                      biodosimetry for protracted radiation exposures as part of
                      the {RENEB} and {EURADOS} {WG}10 2019 exercise},
      journal      = {Scientific reports},
      volume       = {11},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {FZJ-2023-03097},
      pages        = {9756},
      year         = {2021},
      abstract     = {Large-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.},
      cin          = {S-US},
      ddc          = {600},
      cid          = {I:(DE-Juel1)S-US-20090406},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {33963206},
      UT           = {WOS:000656464100007},
      doi          = {10.1038/s41598-021-88403-4},
      url          = {https://juser.fz-juelich.de/record/1010514},
}