DNA damage in leukocytes after internal ex-vivo irradiation of blood with the α-emitter Ra-223

Please always quote using this URN: urn:nbn:de:bvb:20-opus-175596
  • 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 localIrradiation 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.show moreshow less

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Metadaten
Author: Sarah SchumannORCiD, Uta Eberlein, Razan Muhtadi, Michael LassmannORCiD, Harry Scherthan
URN:urn:nbn:de:bvb:20-opus-175596
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin
Language:English
Parent Title (English):Scientific Reports
Year of Completion:2018
Volume:8
Issue:2286
Source:Scientific Reports (2018) 8:2286. DOI: 10.1038/s41598-018-20364-7
DOI:https://doi.org/10.1038/s41598-018-20364-7
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:DNA Breaks; alpha particles; blood; double-stranded; gamma rays; healthy volunteers; humans; leukocytes; radiation effects; radium
Release Date:2019/02/06
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International