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@INPROCEEDINGS{Kriehuber:837946,
      author       = {Kriehuber, Ralf and Dahmen, Volker and Schmitz, Sabine and
                      Unverricht, Marcus and Pomplun, Ekkehard},
      title        = {{G}eno- and {C}ytotoxicity of {DNA}-associated {A}uger
                      {E}lectron emitters},
      reportid     = {FZJ-2017-06707},
      year         = {2017},
      abstract     = {Theoretical considerations, Monte-Carlo simulations and
                      experimental findings suggest that DNA-incorporated Auger
                      electron emitters (AEE) cause primarily complex and
                      clustered DNA lesions. It was previously shown that the
                      shape of AEE-induced cell survival curves resembles that of
                      High-LET irradiation and, therefore, poses the question of
                      an increased biological effectiveness and a separate quality
                      factor for Auger electrons. During electron capture or
                      internal conversion an electron vacancy in an inner atomic
                      shell is created. Filling the electron vacancy by a higher
                      shell electron can initiate a process of non-radiative
                      energy transmission, commonly termed as “Auger effect”.
                      During the process numerous low-energy Auger electrons (up
                      to 27 in the case of Iodine-125) with a short range are
                      emitted leading to energy densities and free radical
                      production in the close vicinity of the emitter exceeding
                      that of a 5 MeV alpha-particle traversing the DNA
                      double-helix. Experimental data demonstrate, that the cyto-
                      and genotoxicity of AEE is comparable to low-LET radiation
                      per unit dose when the AEE is exclusively located in the
                      cytoplasm. However, in case of DNA-incorporation RBEs
                      ranging from 5 – 9 are frequently reported. Employing the
                      alkaline and neutral comet assay, the high DSB/SSB ratio of
                      I-125-iododeoxyuridine derived from Monte-Carlo simulations
                      could be experimentally confirmed. The unique properties of
                      AEE and the possibility to target DNA in a sequence-specific
                      manner using AEE-labeled Triplex-forming oligonucleotides
                      (TFOs) enable to study the repair of complex DNA lesions at
                      defined sites in more detail. A transgenic SCL-II p2RT
                      strain carrying the stably integrated recoverable p2RT
                      vector system harboring a specific triplex target sequence
                      for TFO-p2RT will help to analyze the repair efficiency of
                      complex DNA lesions regarding mutation frequency, mutation
                      type and mutation localization.},
      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)6},
      url          = {https://juser.fz-juelich.de/record/837946},
}