@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} }