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@INPROCEEDINGS{Dahmen:841317,
      author       = {Dahmen, Volker and Kriehuber, Ralf},
      title        = {{C}ytotoxicity and induction of cell cycle arrest in
                      {SCL}-{II} cells after transfection with {I}-125 labeled
                      {T}riplex-{F}orming {O}ligonucleotides},
      reportid     = {FZJ-2017-08406},
      year         = {2012},
      abstract     = {Introduction: Triplex-forming oligonucleotides (TFOs) are
                      able to bind DNA in a sequence specific manner and are a
                      promising tool to manipulate genes or gene regulatory units
                      in a cellular environment. TFOs posses also a therapeutic
                      potential e.g. as a carrier molecule for Alpha- or
                      Auger-Electron-Emitter (AEE) to target specific DNA
                      sequences in tumor cells. We established a method for the
                      effective labeling of TFOs with the AEE iodine-125 (I-125)
                      and studied the influence of labeled TFOs in transfected
                      SCL-II cells with regard to cell survival, appearance of DNA
                      Double-Strand-Breaks (DSB) and the induction of cell cycle
                      arrest.Methods: The TFOs employed were a single binding site
                      TFO, specific for GAPDH and two multi-binding TFOs with
                      several thousand binding sites in the human genome. TFO
                      labeling with I-125 was performed using the primer extension
                      method. Cell survival and DNA DSB frequency in I-125-TFO
                      transfected SCL-II cells were analyzed with the
                      Colony-Forming-Assay and the 53BP1 Assay. Analysis of cell
                      cycle was done after 7-AAD staining by
                      flowcytometry.Results: All three tested TFOs induced a
                      pronounced cytotoxic effect on SCL-II cells. The broadest
                      effect was found for the TFO employing the highest target
                      number in the genome. Furthermore an increased frequency of
                      DSB and a significant cell cycle arrest in G2/M phase 8 h
                      post-transfection could be detected.Conclusion: I-125
                      labeled TFOs with multiple binding sites as well as single
                      binding TFOs do induce a pronounced cytotoxic effect and
                      increase the DSB frequency in SCL-II cells. Additionally
                      there is strong evidence that I-125-labeled TFOs can
                      influence the cell cycle course in transfected SCL-I cells.
                      Funded by the Bundesministerium für Bildung und Forschung
                      (BMBF), Kompetenzverbund Strahlenforschung (KVSF), Project
                      No.: 02NUK005A},
      month         = {Sep},
      date          = {2012-09-17},
      organization  = {15. 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/841317},
}