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

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-i...

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Bibliographic Details
Published in:Scientific reports 2018-02, Vol.8 (1), p.2286-9, Article 2286
Main Authors: Schumann, Sarah, Eberlein, Uta, Muhtadi, Razan, Lassmann, Michael, Scherthan, Harry
Format: Article
Language:English
Subjects:
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14/1
631/80
692/308/53
Alpha Particles
Blood
Blood - radiation effects
Deoxyribonucleic acid
DNA
DNA Breaks, Double-Stranded - radiation effects
DNA damage
Double-strand break repair
Energy transfer
Gamma Rays
Healthy Volunteers
Humanities and Social Sciences
Humans
Irradiation
Leukocytes
Leukocytes - radiation effects
multidisciplinary
Radiation
Radium
Science
Science (multidisciplinary)
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-20364-7