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@INPROCEEDINGS{Dahmen:837949,
      author       = {Dahmen, Volker and Kriehuber, Ralf},
      title        = {{P}rocessing of {C}omplex {DNA} {L}esions in {M}ammalian
                      {C}ells {I}nduced by {I}-125 labeled {T}riplex-{F}orming
                      {O}ligonucleotides},
      reportid     = {FZJ-2017-06710},
      year         = {2017},
      abstract     = {Introduction: Triplex-forming oligonucleotides (TFOs) are
                      known for their ability to bind DNA in a sequence specific
                      manner and are therefore a promising tool to manipulate
                      genes or gene regulatory units. TFOs labeled with the
                      Auger-Electron-Emitter Iodine-125 can induce complex but
                      localized damage to the DNA. Using radionuclide-labeled TFO
                      the subsequent cellular damage was analyzed regarding
                      mutation frequency, mutation type and mutation
                      localization.Methods: The human squameous cell carcinoma
                      cell line SCL-II was used as the wildtype strain SCL-II WT
                      and the transgenic strain SCL-II p2RT. In the conducted
                      experiments the SCL-II WT strain was transiently transfected
                      with an in vitro pre-formed DNA-triplex of the p2RT vector
                      containing the target sequence and its specific TFO, the
                      I-125-TFO p2RT. The transgenic SCL-II p2RT strain carry the
                      stably integrated p2RT vector system harboring the specific
                      triplex target sequence for TFO-p2RT and was, therefore,
                      transfected with the I-125-TFO p2RT only. Efficient delivery
                      of vector + TFO or TFO only was ensured by electroporation
                      with the Nucleofector I system (Lonza GmbH, Basel). After
                      storage at -150°C for decay accumulation the samples were
                      analyzed for mutation frequency, type and localization using
                      blue/white screening and sequencing.Results: In the SCL-II
                      WT cell line an almost four fold increased mutation
                      frequency at the target region on the p2RT vector was found
                      when compared to the negative controls. In contrast, the
                      SCL-II p2RT transgenic strain did not show a significant
                      increase of the mutation frequency in comparison to the
                      negative controls. Sequencing revealed that most mutants
                      displayed large deletions of more than 100 bp located at the
                      TFO p2RT target site. Conclusions: The local complex DNA
                      damage induced by the decay of the TFO delivered Iodine-125
                      is likely to be accountable for the increased mutation rate
                      in the SCL-II WT cells. Since this increase could not be
                      detected in the SCL-II p2RT transgenic strain it can be
                      hypothesized that the site-specific triplex formation
                      between I-125-TFO p2RT and its target sequence is inhibited
                      to some extent in the cellular environment.},
      month         = {Sep},
      date          = {2017-09-17},
      organization  = {Joint Meeting of the European
                       Radiation Research Society and the
                       Society for Biological Radiation
                       Research, Essen (Germany), 17 Sep 2017
                       - 21 Sep 2017},
      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/837949},
}