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@INPROCEEDINGS{Schmitz:188031,
      author       = {Schmitz, Sabine and Oskamp, Dominik and Pomplun, Ekkehard
                      and Kriehuber, Ralf},
      title        = {{C}hromosome aberrations induced by the {A}uger emitter
                      {I}-125},
      reportid     = {FZJ-2015-01516},
      year         = {2014},
      abstract     = {Introduction: DNA-associated Auger-electron emitters (AEE)
                      induce cellular damage leading to high-LET type cell
                      survival curves and possess enhanced relative biological
                      effectiveness. DNA dsb induced by Iodine-125-deoxyuridine
                      (I-125-UdR) decays are claimed to be very complex, thus
                      efficiently leading to cell transformation, gene mutation
                      and induction of chromatid aberrations. To elucidate the
                      assumed genotoxic potential of DNA-associated AEE,
                      chromosomal/chromatid aberrations were analyzed in
                      I-125-UdR-exposed human peripheral blood lymphocytes
                      (PBL).Methods: PBL were isolated from whole blood and
                      stimulated with chromosome medium containing
                      phytohaemagglutinin (PHA). After 24 h cultures were labeled
                      with I-125-UdR for 18 h (0.25-4.5 kBq/ml) during the S-phase
                      of the cell cycle. After removal of radioactive medium and
                      washing steps, cells were re-cultured in stimulation medium
                      for further 24 h. Colcemid was added 5.5 h before harvest of
                      cells followed by fixation for aberrations at 71.5 h
                      post-stimulation. All slides were stained with 10 $\%$
                      Giemsa, and 100 metaphases were analyzed microscopically for
                      each dose point.Results: After 18 h labeling with I-125-UdR
                      the cell cycle distribution is severely disturbed.
                      Furthermore, $40\%$ of PBL are fully labelled and $20\%$
                      show a moderate uptake of I-125-UdR. I-125-UdR primarily
                      induces chromatid-type aberrations. PBL reveal a very broad
                      dose-dependent response spectrum: equal numbers of cells
                      have either no aberration, or display a moderate aberration
                      level (1-9 aberrations). Few cells exhibit a high aberration
                      score (> 10 aberrations). A dose-dependent increase of
                      aberrations is measured in the range of 0.2 to 2 Gy,
                      followed by a plateau between 2 and 4.5 Gy. The data
                      indicate that even the lowest dose of 0.2 Gy leads to
                      significant damage in PBL and to a 4.5-fold increase of
                      aberrations compared to the controls. Furthermore, a
                      dose-dependent increase of cell death is
                      observed.Conclusions: I-125-UdR has a very strong genotoxic
                      capacity in human PBL even at very low doses of about 0.2
                      Gy. Efficiently labeled cells displaying a prolonged cell
                      cycle compared to moderate labeled cells, and cell death
                      contribute substantially to the desynchronisation of the
                      cell cycle. In summary, it can be concluded that every
                      fourth intracellular I-125 decay give rise to a single
                      chromosome aberration.},
      month         = {Sep},
      date          = {2014-09-12},
      organization  = {11th International Symposium on
                       Chromosomal Aberrations, Rhodes
                       (Greek), 12 Sep 2014 - 14 Sep 2014},
      subtyp        = {Invited},
      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)6},
      url          = {https://juser.fz-juelich.de/record/188031},
}