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@INPROCEEDINGS{Dahmen:255694,
      author       = {Dahmen, Volker and Reiter, Stefan and Pomplun, Ekkehard and
                      Kriehuber, Ralf},
      title        = {{I}odine-125-labeled {DNA}-{T}riplex-forming
                      oligonucleotides reveal increased cyto- and genotoxic
                      effectiveness compared to {P}hosphorus-32 and external
                      γ-irradiation},
      reportid     = {FZJ-2015-05826},
      year         = {2015},
      abstract     = {Introduction: The efficacy of DNA-targeting radionuclide
                      therapies might be strongly enhanced by employing short
                      range particle emitter. To determine the gain of the
                      biological impact per decay and radiation dose the
                      biological effectiveness of the Auger electron emitter I-125
                      was investigated and compared to the ß--emitter P-32 and
                      external homogeneous high dose rate γ-irradiation.Methods:
                      Triplex-forming oligonucleotides (TFO) bind to the DNA
                      double helix in a sequence specific manner and are therefore
                      a suitable carrier for Auger electron emitter to damage
                      exclusively targeted DNA sequences [1]. Clonogenicity
                      (colony-forming assay; CFA) and induction of DNA double
                      strand breaks (DSB; 53BP1 foci assay) were investigated in
                      SCL-II cells after exposure to I-125- or P-32-labeled TFO
                      for different numbers of accumulated decays and were
                      compared to external γ-irradiation (Cs-137; 0.7 Gy/min).
                      The used TFO targeted a DNA sequence located in the
                      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. Point
                      kernel calculations were employed for dosimetry on
                      subcellular level.Results: I-125-labeled TFO were shown to
                      induce a pronounced decrease in cell survival and a marked
                      increase of DSB with increasing numbers of accumulated
                      decays per cell. Reduction in cell survival as measured in
                      the CFA reached the D37 value at ~ 350 cumulated decays per
                      cell, equivalent to ~ 1.2 Gy cell nucleus dose. P-32 labeled
                      TFO displayed a weak cell killing ability and caused a small
                      increase of 53BP1 foci up to ~ 4000 accumulated decays per
                      cell, equivalent to ~ 1 Gy cell nucleus dose. The impact of
                      P-32 was comparable to external γ-irradiation.Conclusions:
                      The reduction of cell survival and the increase of DNA
                      damage proved to be much more pronounced in I-125-TFO
                      exposed cells in comparison to P-32-labeled TFO per decay
                      and per dose unit. This finding might be well 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
                      highly complex DNA lesions, overcharging the cellular
                      DNA-damage repair mechanism. The similar biological
                      effectiveness of P-32-TFO exposure and external
                      γ-irradiation proves the validity of the performed dose
                      calculation on cellular level.[1] Dahmen V, Kriehuber R. Int
                      J Radiat Biol. 2012 Dec;88(12):972-9Supported by BMBF Grant
                      02NUK005},
      month         = {May},
      date          = {2015-05-20},
      organization  = {8th Auger Symposium Kyoto 2015, Kyoto
                       (Japan), 20 May 2015 - 22 May 2015},
      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/255694},
}