@article{SchumannEberleinMuhtadietal.2018,
  author    = {Schumann, Sarah and Eberlein, Uta and Muhtadi, Razan and Lassmann, Michael and Scherthan, Harry},
  title     = {DNA damage in leukocytes after internal ex-vivo irradiation of blood with the α-emitter Ra-223},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {2286},
  doi       = {10.1038/s41598-018-20364-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175596},
  year      = {2018},
  abstract  = {Irradiation with high linear energy transfer α-emitters, like the clinically used Ra-223 dichloride, severely damages cells and induces complex DNA damage including closely spaced double-strand breaks (DSBs). As the hematopoietic system is an organ-at-risk for the treatment, knowledge about Ra-223-induced DNA damage in blood leukocytes is highly desirable. Therefore, 36 blood samples from six healthy volunteers were exposed ex-vivo (in solution) to different concentrations of Ra-223. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the decay, ranging from 0 to 142 mGy. γ-H2AX + 53BP1 co-staining and analysis was performed in leukocytes isolated from the irradiated blood samples. For DNA damage quantification, leukocyte samples were screened for occurrence of α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values, being in agreement with a negligible β-contribution (3.7\%) to the total absorbed dose to the blood. Our calibration curve will contribute to the biodosimetry of Ra-223-treated patients and early after incorporation of α-emitters.},
  language  = {en}
}
@article{ScherthanLeeMausetal.2019,
  author    = {Scherthan, Harry and Lee, Jin-Ho and Maus, Emanuel and Schumann, Sarah and Muhtadi, Razan and Chojowski, Robert and Port, Matthias and Lassmann, Michael and Bestvater, Felix and Hausmann, Michael},
  title     = {Nanostructure of clustered DNA damage in leukocytes after in-solution irradiation with the alpha emitter Ra-223},
  series = {Cancers},
  volume    = {11},
  journal   = {Cancers},
  number    = {12},
  issn      = {2072-6694},
  doi       = {10.3390/cancers11121877},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193038},
  year      = {2019},
  abstract  = {Background: Cancer patients are increasingly treated with alpha-particle-emitting radiopharmaceuticals. At the subcellular level, alpha particles induce densely spaced ionizations and molecular damage. Induction of DNA lesions, especially clustered DNA double-strand breaks (DSBs), threatens a cell's survival. Currently, it is under debate to what extent the spatial topology of the damaged chromatin regions and the repair protein arrangements are contributing. Methods: Super-resolution light microscopy (SMLM) in combination with cluster analysis of single molecule signal-point density regions of DSB repair markers was applied to investigate the nano-structure of DNA damage foci tracks of Ra-223 in-solution irradiated leukocytes. Results: Alpha-damaged chromatin tracks were efficiently outlined by γ-H2AX that formed large (super) foci composed of numerous 60-80 nm-sized nano-foci. Alpha damage tracks contained 60-70\% of all γ-H2AX point signals in a nucleus, while less than 30\% of 53BP1, MRE11 or p-ATM signals were located inside γ-H2AX damage tracks. MRE11 and p-ATM protein fluorescent tags formed focal nano-clusters of about 20 nm peak size. There were, on average, 12 (±9) MRE11 nanoclusters in a typical γ-H2AX-marked alpha track, suggesting a minimal number of MRE11-processed DSBs per track. Our SMLM data suggest regularly arranged nano-structures during DNA repair in the damaged chromatin domain.},
  language  = {en}
}