% 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{Dahmen:839897,
      author       = {Dahmen, Volker and Kriehuber, Ralf},
      title        = {{TRIPLEX}-{FORMING} {OLIGONUCLEOTIDES} {AS} {A} {CARRIER}
                      {FOR} {AUGER} {ELECTRON} {EMITTER}: {STUDIES} {ON}
                      {CYTOTOXICITY} {AND} {ON} {SPECIFIC} {GENE} {EXPRESSION}
                      {ALTERATIONS} {CAUSED} {BY} 125-{I}-{LABELLED} {TFOS}},
      reportid     = {FZJ-2017-07475},
      year         = {2011},
      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 tumour cells. We established a method for the
                      effective labelling of TFOs with the AEE iodine-125 (I-125)
                      and studied the influence of labelled TFO with regard to
                      cell survival and appearance of DNA Double-Strand-Breaks
                      (DSB). Furthermore the ability of TFOs to alter gene
                      expression of targeted genes was examined.Methods: TFOs
                      specific for the genes BCL2, GAPDH and BRCA1 were designed
                      employing TFO Target Sequence Search (Univ. of Texas). TFO
                      labelling with I-125 was performed using the primer
                      extension method. Formation of DNA triplexes was visualized
                      with MS Imaging Plates employing a FLA-5000 Imaging System
                      (Fujifilm) and electrophoretic mobility shift assay (EMSA).
                      Cell survival and DNA DSB frequency in SCL-II cells after
                      transfection with I-125-labelled Multi-Binding-Site (MBS)
                      TFO (~ 7000 binding sites) were analyzed with the
                      Colony-Forming Assay and the 53BP1-Foci Assay. SCL-II cells
                      transfected with TFOs binding to single DNA targets in
                      specific genes were analyzed for gene expression alterations
                      of the targeted genes with qRT-PCR on a 7500 Real Time PCR
                      System (Applied Biosystems).Results: The MBS
                      I-125-labelled-TFO transfected SCL-II cells showed a
                      reduction of colony forming ability of ~ 45 $\%$ and the
                      number of 53BP1-Foci was ~ 1.5-times increased when compared
                      to sham-transfected negative control. The transfection with
                      single binding site I-125-labelled-TFOs lead to a 1.7-times
                      increased expression for BCL2 and a 0.5-times reduced
                      expression for GAPDH. No altered gene expression was
                      detected for BRCA1.Conclusions: I-125-labelled MBS TFOs have
                      a pronounced cytotoxic effect and induce DNA DSB in SCL-II
                      cells. Single gene targeting TFOs can alter gene expression
                      in a gene-specific manner.Funded by the Kompetenzverbund
                      Strahlenforschung (KVSF), Bundesministerium für Bildung und
                      Forschung (BMBF), Project No.: 02NUK005A},
      month         = {Sep},
      date          = {2011-09-13},
      organization  = {14. Jahrestagung der Gesellschaft für
                       Biologische Strahlenforschung,
                       Rheinbach (Germany), 13 Sep 2011 - 16
                       Sep 2011},
      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/839897},
}