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@INPROCEEDINGS{Knops:839983,
      author       = {Knops, Katja and Boldt, Sonja and Wolkenhauer, Olaf and
                      Kriehuber, Ralf},
      title        = {{G}ene {E}xpression {A}nalysis in {H}uman {P}eripheral
                      {B}lood {L}ymphocytes for {B}iodosimetric {A}pplications
                      after {L}ow and {H}igh {D}ose {G}amma-{I}rradiation},
      reportid     = {FZJ-2017-07553},
      year         = {2012},
      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). Subsequently RNA and
                      proteins were isolated and RNA was applied for processing
                      whole human genome microarrays (Agilent) to analyze
                      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 and for two genes
                      in the low dose range the observed radiation-induced gene
                      expression profiles were confirmed and validated by qRT-PCR
                      measurements in pooled and non-pooled samples. Additionally,
                      qRT-PCR analysis revealed that the radiation dose predictive
                      genes are highly radiation-specific 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 Bundesministerium für Bildung
                      und Forschung (BMBF), Project No.: 02NUK005A and 02NUK005D
                      and supported by Kompetenzverbund Strahlenforschung (KVSF)},
      month         = {Oct},
      date          = {2012-10-15},
      organization  = {39th Annual Meeting of the European
                       Radiation Research Society, Vietri sul
                       Mare (Italy), 15 Oct 2012 - 19 Oct
                       2012},
      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/839983},
}