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@INPROCEEDINGS{Knops:839900,
      author       = {Knops, Katja and Boldt, Sonja and Wolkenhauer, Olaf and
                      Kriehuber, Ralf},
      title        = {{RADIATION}-{SPECIFIC} {GENE} {EXPRESSION} {CHANGES} {IN}
                      {HUMAN} {PBL} {AFTER} {EX} {VIVO} {IRRADIATION} {SUITABLE}
                      {FOR} {RADIATION} {BIODOSIMETRY}},
      reportid     = {FZJ-2017-07478},
      year         = {2011},
      abstract     = {Introduction: In case of a large-scale radiation accident
                      with involvement of individuals without physical dosimeters
                      it is important to identify individuals who have received a
                      moderate to high radiation dose to ensure proper medical
                      care. As current methods are time-consuming, a fast and
                      reliable method based on gene expression alterations is
                      developed.Methods: Human blood of 3 male and 3 female
                      healthy donors, belonging to 3 different age classes, was
                      irradiated ex vivo with 0, 0.02, 0.1, 0.5, 1, 2 and 4 Gy
                      (γ-rays, Cs-137). Peripheral blood lymphocytes (PBL) were
                      isolated and cultured for 6, 24 and 48 h in the medium- and
                      high dose range (0.5 – 4 Gy) and for 24 and 48 h after low
                      dose irradiation (0.02 and 0.1 Gy). At these times RNA and
                      proteins were isolated and RNA was applied for processing
                      whole human genome DNA-microarrays to analyse expression
                      profiles. In the medium- and high dose range the most robust
                      altered genes were selected for further qRT-PCR and protein
                      expression analysis. To examine the radiation-specificity of
                      the candidate genes, PBL were exposed to the DNA-damaging
                      agents Paracetamol (25 and 200 µg/ml) and Mitomycin C (0.1
                      and 0.4 µg/ml) for 6, 24 and 48 h and gene expression was
                      accordingly analyzed.Results: By a p-value and fold-change
                      driven gene selection 9 genes were identified in the low
                      dose range and 16 genes in the medium- and high dose range
                      allowing a radiation dose prediction accuracy of $96\%$
                      independently on the time-point post irradiation up to 48 h.
                      For 6 predictive genes in the medium- and high dose range
                      qRT-PCR measurements based on pooled and non-pooled
                      irradiated samples additionally validated the observed
                      radiation-induced gene expression alterations. Furthermore,
                      qRT-PCR analysis showed that the strong up-regulation of
                      these genes is highly radiation-specific as the
                      up-regulation after irradiation was much more pronounced
                      when compared to exposure with Paracetamol or Mitomycin C.
                      Protein expression analysis showed only for two genes a weak
                      correlation between gene and protein expression after
                      irradiation. Conclusion: In vitro gene expression analysis
                      in human PBL based on whole human DNA-microarray data
                      allowed identifying a rather small set of radiation dose
                      predictive and radiation-specific genes with a high
                      potential for biodosimetric applications in vivo after low-,
                      medium and high dose exposure. Funded by Kompetenzverbund
                      Strahlenforschung (KVSF), Bundesministerium für Bildung und
                      Forschung (BMBF), Project No.: 02NUK005A and 02NUK005B},
      month         = {Sep},
      date          = {2011-09-13},
      organization  = {14. Jahrestagung der Gesellschaft für
                       Biologische Strahlenforschung,
                       Rheinbach (Germany), 13 Sep 2011 - 16
                       Sep 2011},
      subtyp        = {After Call},
      cin          = {S-US},
      cid          = {I:(DE-Juel1)S-US-20090406},
      pnm          = {899 - ohne Topic (POF3-899)},
      pid          = {G:(DE-HGF)POF3-899},
      typ          = {PUB:(DE-HGF)24},
      url          = {https://juser.fz-juelich.de/record/839900},
}