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@INPROCEEDINGS{Unverricht:841305,
      author       = {Unverricht, Marcus and Oskamp, Dominik and Kriehuber, Ralf},
      title        = {{C}haracterization of cell cycle perturbances after
                      exposure to {I}-123-iododeoxyuridine},
      reportid     = {FZJ-2017-08395},
      year         = {2012},
      abstract     = {Introduction: Due to the numerous short-range electrons
                      ejected during a single decay of an Auger electron emitter
                      (AEE), the biological effectiveness of AEE depends strongly
                      on intracellular location. DNA-associated AEE possess the
                      highest biological effectiveness per decay and are presumed
                      to cause complex DNA lesions and cell cycle perturbances.
                      The main goal of the study was to determine the average
                      number of decay per cell necessary to induce a pronounced
                      G2/M-arrest in human T-lymphoma Jurkat cells.Material $\&$
                      Methods: Synchronized Jurkat cells were exposed to
                      I-123-iododeoxyuridine (I-123-UdR, 1-50 kBq/ml) for 20 h and
                      co-labeled with 5-ethynyl-2'-deoxyuridine (EdU). Cell cycle
                      was subsequently analyzed by flowcytometry (FACSCanto II,
                      FACSDiva software, BD). General cellular uptake and
                      DNA-incorporation of I-123-UdR in isolated DNA (DNeasy Blood
                      $\&$ Tissue Kit; QIAGEN) was determined by gamma-counting
                      (Perkin Elmer). Results: The percentage of G2/M-cells which
                      are labeled with EdU increased 20 h after exposure to
                      I-123-UdR/EdU from $26\%$ in the control to $57\%,$ $66\%$
                      and $63\%$ at 111, 417 and 3255 accumulated decays per cell,
                      respectively. Simultaneously, the percentages of
                      post-mitotic G1-cells which are fully labeled with EdU
                      decreased from $38\%$ in the control to $10\%,$ $1\%$ and
                      $3\%$ at 111, 417 and 3255 accumulated decays per cell,
                      respectively. Approximately $93\%$ of the cells were labeled
                      with I-123-UdR/EdU after 20 h of exposure whilst ~ $90\%$ of
                      the I-123-UdR activity was located in the DNA. Conclusions:
                      On average one decay every ~180 seconds of I-123 occurring
                      in the genome of a Jurkat cell induces a massive
                      G2/M-arrest. This coincides very well with observations in
                      I-125-UdR exposed SCL-II cells, showing massive and
                      persistent G2/M-arrest at similar decay rates. Decay rates
                      as low as one decay every 12 minutes per genome induce
                      massive but transient G2/M-arrest suggesting different
                      damage levels for induction and escape of the G2/M arrest in
                      human cells.Funded by Bundesministerium für Bildung und
                      Forschung (BMBF), Project No.: 02NUK005A},
      month         = {Sep},
      date          = {2012-09-17},
      organization  = {15th Annual Meeting of the German
                       Society for Biological Radiation
                       Research15. Jahrestagung der
                       Gesellschaft für Biologische
                       Strahlenforschung, München (Germany),
                       17 Sep 2012 - 20 Sep 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/841305},
}