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@ARTICLE{Dahmen:808536,
      author       = {Dahmen, Volker 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},
      journal      = {International journal of radiation biology},
      volume       = {92},
      number       = {11},
      issn         = {0955-3002},
      address      = {London},
      publisher    = {Taylor $\&$ Francis},
      reportid     = {FZJ-2016-02274},
      pages        = {679-685},
      year         = {2016},
      abstract     = {PURPOSE: The efficacy of DNA-targeting radionuclide
                      therapies might be strongly enhanced by employing short
                      range particle-emitters. However, the gain of effectiveness
                      is not yet well substantiated. We compared the Auger
                      electron emitter I-125 to the ß--emitter P-32 in terms of
                      biological effectiveness per decay and radiation dose when
                      located in the close proximity to DNA using DNA
                      Triplex-forming oligonucleotides (TFO). The clonogenicity
                      and the induction of DNA double-strand breaks (DSB) were
                      investigated in SCL-II cells after exposure to P-32- or
                      I-125-labeled TFO targeting the glyceraldehyde 3-phosphate
                      dehydrogenase (GAPDH) gene and after external homogeneous
                      exposure to gamma-rays as reference radiation.MATERIALS AND
                      METHODS: TFO were labeled with P-32 or I-125 using the
                      primer extension method. Cell survival was analyzed by
                      colony-forming assay and DNA damage was assessed by
                      microscopic quantification of protein 53 binding protein 1
                      (53BP1) foci in SCL-II cells.RESULTS: I-125-TFO induced a
                      pronounced decrease of cell survival (D37 at ∼360
                      accumulated decays per cell, equivalent to 1.22 Gy cell
                      nucleus dose) and a significant increase of 53BP1 foci with
                      increasing decays. The P-32-labeled TFO induced neither a
                      strong decrease of cell survival nor an increase of 53BP1
                      foci up to ∼4000 accumulated decays per cell, equivalent
                      to ∼1 Gy cell nucleus dose. The RBE for I-125-TFO was in
                      the range of 3-4 for both biological endpoints.CONCLUSIONS:
                      I-125-TFO proved to be much more radiotoxic than P-32-TFO
                      per decay and per unit dose although targeting the same
                      sequence in the GAPDH gene. This 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 DNA repair
                      mechanisms.},
      cin          = {S-US},
      ddc          = {570},
      cid          = {I:(DE-Juel1)S-US-20090406},
      pnm          = {899 - ohne Topic (POF3-899)},
      pid          = {G:(DE-HGF)POF3-899},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000388629800010},
      doi          = {10.3109/09553002.2016.1160157},
      url          = {https://juser.fz-juelich.de/record/808536},
}