% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@INPROCEEDINGS{Katja:839982,
      author       = {Katja, Knops and Boldt, Sonja and Wolkenhauer, Olaf and
                      Kriehuber, Ralf},
      title        = {{T}ime-dependent {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-2017-07552},
      year         = {2012},
      abstract     = {Time-dependent Gene Expression Analysis in Human Peripheral
                      Blood Lymphocytes for Biodosimetric Applications after Low
                      and High Dose Gamma-Irradiation Katja Knops1, Sonja Boldt2,
                      Olaf Wolkenhauer2, Ralf Kriehuber1 1Department of Safety and
                      Radiation Protection, Forschungszentrum Jülich, D-52425
                      Jülich, Germany, k.knops@fz-juelich.de2Department of
                      Computer Science, Systems Biology and Bioinformatics Group,
                      University of Rostock, D-18051 Rostock, Germany,
                      boldt@informatik.uni-rostock.deIntroduction: 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         = {May},
      date          = {2012-05-13},
      organization  = {13th International Congress of the
                       International Radiation Protection
                       Association, Glasgow (UK), 13 May 2012
                       - 18 May 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/839982},
}