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@INPROCEEDINGS{Dahmen:841326,
      author       = {Dahmen, Volker and Kriehuber, Ralf},
      title        = {{C}ytotoxic effects and specific gene expression
                      alterations induced by {I}-125-labelled {T}riplex-forming
                      oligonucleotides},
      reportid     = {FZJ-2017-08411},
      year         = {2011},
      abstract     = {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 potential for radiotherapy
                      e.g. as a carrier 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.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. Cell survival and DNA DSB frequency in SCL-II cells
                      after transfection with a I-125-labelled Multi-Binding-Site
                      (MBS) TFO (~ 7000 binding sites) were analyzed with the
                      Colony-Forming Assay respectively with 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.The MBS
                      I-125-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-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.I-125-labelled MBS TFOs induce a pronounced cytotoxic
                      effect in SCL-II cells. Single gene targeting TFOs alter
                      gene expression in a gene-specific manner.Funded by
                      Kompetenzverbund Strahlenforschung (KVSF), Bundesministerium
                      für Bildung und Forschung (BMBF), Project No.: 02NUK005A},
      month         = {Aug},
      date          = {2011-08-24},
      organization  = {7th International Symposium on
                       Physical, Molecular, Cellular and
                       Medical Aspects of Auger, Jülich
                       (Germany), 24 Aug 2011 - 26 Aug 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/841326},
}