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@ARTICLE{Abend:811945,
      author       = {Abend, M. and Badie, C. and Quintens, R. and Kriehuber, R.
                      and Manning, G. and Macaeva, E. and Njima, M. and Oskamp, D.
                      and Strunz, S. and Moertl, S. and Doucha-Senf, S. and
                      Dahlke, S. and Menzel, J. and Port, M.},
      title        = {{E}xamining {R}adiation-{I}nduced {I}n {V}ivo and {I}n
                      {V}itro {G}ene {E}xpression {C}hanges of the {P}eripheral
                      {B}lood in {D}ifferent {L}aboratories for {B}iodosimetry
                      {P}urposes: {F}irst {RENEB} {G}ene {E}xpression {S}tudy},
      journal      = {Radiation research},
      volume       = {185},
      number       = {2},
      issn         = {1938-5404},
      address      = {Great Falls, Va.},
      publisher    = {Radiation Research Society},
      reportid     = {FZJ-2016-04255},
      pages        = {109 - 123},
      year         = {2016},
      abstract     = {The 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.},
      cin          = {S-US},
      ddc          = {610},
      cid          = {I:(DE-Juel1)S-US-20090406},
      pnm          = {899 - ohne Topic (POF3-899)},
      pid          = {G:(DE-HGF)POF3-899},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000370734200002},
      doi          = {10.1667/RR14221.1},
      url          = {https://juser.fz-juelich.de/record/811945},
}