% 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:837959,
      author       = {Dahmen, Volker and Reiter, Stefan and Pomplun, Ekkehard and
                      Kriehuber, Ralf},
      title        = {{E}nhanced cyto- and genotoxic effects of {A}uger electron
                      emitter-labeled {DNA}-{T}riplex-forming oligonucleotides in
                      vitro},
      reportid     = {FZJ-2017-06720},
      year         = {2014},
      abstract     = {The efficacy of DNA-targeting radionuclide therapies might
                      be strongly enhanced by employing short range
                      particleemitter.However, the therapeutic use of
                      radionuclides requests a thorough radiation dosimetry
                      especially whenshort-range particles are released. In this
                      study we compared the ß-emitter P-32 and the Auger electron
                      emitter I-125in terms of biological effectiveness per decay
                      and per unit dose when located in the close proximity to the
                      DNA byusing Triplex-forming oligonucleotides (TFO).TFO bind
                      to the DNA double helix in a sequence specific manner.
                      Therefore, TFO seem to be a suitable carrier
                      forradionuclides emitting short-range electrons to damage
                      exclusively targeted DNA sequences. We
                      investigatedclonogenicity (colony-forming assay; CFA) in the
                      human squamous carcinoma cell line II (SCL-II) and the
                      induction ofDNA double strand breaks (DSB; 53BP1 foci assay)
                      after exposure with P-32 or I-125 labeled TFO for
                      differentnumbers of accumulated decays. The employed TFO
                      targeted a specific DNA sequence located in the
                      glyceraldehyde3-phosphate dehydrogenase (GAPDH)
                      gene.Results: I-125-labeled TFO binding to single targets
                      were shown to induce a pronounced decrease in cell survival
                      andan increase of DSB with increasing numbers of accumulated
                      decays per cell. The reduction in cell survival asmeasured
                      in the CFA reached the D37 value at ~ 350 accumulated decays
                      per cell, equivalent to ~ 1.2 Gy cellnucleus dose. Using the
                      same TFO but labeled with P-32 revealed neither a
                      significant decrease of the survivalfraction nor an increase
                      of the DSB rate in SCL-II cells up to ~ 4,000 accumulated
                      decays per cell which is equivalentto ~ 1 Gy cell nucleus
                      dose.Summary $\&$ Conclusions: The reduction of cell
                      survival and the increase of DNA damage proved to be much
                      morepronounced in I-125-TFO transfected cells than observed
                      after exposure with the P-32-labeled TFO per decay and
                      perdose unit. This can be explained by the high number of
                      low energy Auger electrons emitted by I-125 per
                      decay,leading to a high ionization density in the immediate
                      vicinity of the decay site, probably producing very complex
                      DNAlesions, overcharging the cellular DNA-repair
                      mechanisms.},
      month         = {Oct},
      date          = {2014-10-18},
      organization  = {27th Annual Congress of the European
                       Association of Nuclear Medicine and 5th
                       International Symposium on Targeted
                       Radionuclide-therapy and Dosimetry,
                       Göteborg (Schweden), 18 Oct 2014 - 22
                       Oct 2014},
      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)6},
      url          = {https://juser.fz-juelich.de/record/837959},
}