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@INPROCEEDINGS{Dahmen:865160,
      author       = {Dahmen, Volker and Schmitz, Sabine and Kriehuber, Ralf},
      title        = {{I}nduction of specific chromosomal rearrangements by
                      targeting sensitive genomic loci using{I}-125-labeled
                      {T}riplex-forming oligonucleotides},
      reportid     = {FZJ-2019-04706},
      year         = {2019},
      abstract     = {Triplex-Forming-oligonucleotides (TFO) bind DNA in a
                      sequence-specific manner and possess therapeutic potential
                      e.g. as a carrier-molecule for Auger-Electron-Emitter (AEE)
                      targeting specific DNA sequences in tumor cells. We
                      established a method for the labeling of TFO with the AEE
                      Iodine-125 (125I) and analyzed the influence of 125I-labeled
                      TFO in SCL-II cells on gene expression, translocation
                      frequency and protein expression of the human BCL2 gene.
                      TFO-BCL2 binds to the BCL2 gene upstream of the 3´-end. TFO
                      labeling with 125I was performed using the
                      primer-extension-method. SCL-II cells were transfected with
                      TFO via electroporation and subsequently stored at -150°C
                      for decay accumulation. SCL-II cells transfected with
                      125I-labeled multi-binding TFO or non-labeled TFO-BCL2
                      served as controls. Monitoring of BCL2 translocations was
                      done with Fluorescence-In-Situ-Hybridization (FISH). The
                      utilized FISH-probes were designed to detect a
                      characteristic t(14;18) translocation of the BCL2 gene,
                      leading to an overexpression of BCL-2. Gene expression
                      levels were measured via qRT-PCR. Verification of gene
                      expression on the protein level was analyzed by Western
                      blotting. The relative gene expression of BCl-2 in
                      125I-TFO-BCL2 transfected cells showed a significant
                      up-regulation and analysis of the BCL2 t(14;18)
                      translocation frequency revealed a significant ~ 1.8-fold
                      increase. This increase was not reflected on the protein
                      level.We conclude that 125I decays within the BCL2 gene
                      facilitate the t(14;18) chromosomal translocation and that
                      the increased translocation frequency contributes to the
                      observed enhanced BCL-2 gene expression. Funded by
                      Bundesministerium für Bildung und Forschung (BMBF), Grant
                      02NUK005A and 02NUK043A},
      month         = {Sep},
      date          = {2019-09-09},
      organization  = {51st Annual Meeting of the Association
                       for Radiation Protection, Würzburg
                       (Germany), 9 Sep 2019 - 12 Sep 2019},
      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/865160},
}