TY  - JOUR
A1  - Schumann, Sarah
A1  - Eberlein, Uta
A1  - Muhtadi, Razan
A1  - Lassmann, Michael
A1  - Scherthan, Harry
T1  - DNA damage in leukocytes after internal ex-vivo irradiation of blood with the α-emitter Ra-223
JF  - Scientific Reports
N2  - 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.
KW  - alpha particles
KW  - blood
KW  - DNA Breaks
KW  - double-stranded
KW  - gamma rays
KW  - healthy volunteers
KW  - humans
KW  - leukocytes
KW  - radiation effects
KW  - radium
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175596
VL  - 8
IS  - 2286
ER  -