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@INPROCEEDINGS{Unverricht:188709,
      author       = {Unverricht, Marcus and Giesen and Pomplun, Ekkehard and
                      Kriehuber, Ralf},
      title        = {{G}ene expression analysis after exposure to
                      {I}-123-iododeoxyuridine, γ-rays and α-particles},
      reportid     = {FZJ-2015-02033},
      year         = {2014},
      abstract     = {Gene expression analysis was carried out in human
                      p53-deficient T-lymphoma Jurkat cells in order to identify
                      robust candidate genes showing significant gene expression
                      alterations allowing the discrimination of radiation
                      qualities.Equi-effect radiation doses, i.e. radiation doses
                      and exposure conditions causing the same biological effect
                      level, were determined with regard to micronucleus
                      formation, γ-H2AX foci signal intensity and apoptosis
                      induction after γ-irradiation (Cs-137; dose range: 0.8-10
                      Gy), α-particle exposure (Am-241; dose range: 0.1-1 Gy) and
                      exposure to the Auger electron emitter I-123 as
                      I-123-iododeoxyuridine (I-123-UdR; activity range: 4-200 kBq
                      per 10E6 cells). I-123-UdR was incorporated into the DNA for
                      20 h. Absorbed radiation dose was assessed based on
                      accumulated decays, point-kernel calculations and the 3-D
                      morphology of the cells. Gene expression analysis was
                      performed employing whole human genome DNA-microarrays
                      (Agilent) after exposure to equi-effect radiation doses of
                      all three investigated radiation qualities. RNA for gene
                      expression analysis was isolated 6 and 24 h post-exposure.
                      Only genes showing a >1.5-fold change of expression vs.
                      non-irradiated control were further analyzed for
                      significance. Potential candidate genes for the
                      discrimination of radiation quality have to show (i) a
                      significant expression change after exposure to a specific
                      radiation quality and (ii) display no altered gene
                      regulation (1-fold ± 0.1) or even a conversely (>1.1-fold)
                      regulation in response to exposure to the other radiation
                      qualities investigated. Gene expression of all selected
                      candidate genes was validated via qRT-PCR. Biological
                      processes and pathways of significantly regulated genes were
                      subsequently analyzed. At equi-effect doses the results of
                      the gene expression analysis showed that 359, 598 and 1339
                      genes are significantly regulated after exposure to
                      I-123-UdR, α-particles and γ-rays, respectively. Applying
                      our stringent requirements for candidate genes, we
                      identified only 4, 1 and 1 gene(s) allowing the reliable and
                      robust discrimination between γ- vs. I-123-UdR-exposition,
                      γ- vs. α-radiation and α- vs. I-123-UdR-exposition,
                      respectively. γ-rays induce pronounced alterations in gene
                      expression in Jurkat cells when compared to I-123-UdR and
                      α-particles at equi-effect radiation doses. In vitro gene
                      expression analysis in Jurkat cells might suggest that the
                      discrimination of different radiation qualities by means of
                      gene expression is possible.Funded by Bundesministerium für
                      Bildung und Forschung (BMBF), Project No.: 02NUK005A},
      month         = {Sep},
      date          = {2014-09-14},
      organization  = {41th Annual Meeting of the European
                       Radiation Research Society, Rhodes
                       (Greece), 14 Sep 2014 - 19 Sep 2014},
      subtyp        = {After Call},
      cin          = {S-US},
      cid          = {I:(DE-Juel1)S-US-20090406},
      pnm          = {899 - ohne Topic (POF2-899)},
      pid          = {G:(DE-HGF)POF2-899},
      typ          = {PUB:(DE-HGF)6},
      url          = {https://juser.fz-juelich.de/record/188709},
}