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  - 
TY  - JOUR
A1  - Schuhmann, Sarah
A1  - Eberlein, Uta
A1  - Müller, Jessica
A1  - Scherthan, Harry
A1  - Lassmann, Michael
T1  - Correlation of the absorbed dose to the blood and DNA damage in leukocytes after internal ex-vivo irradiation of blood samples with Ra-224
JF  - EJNMMI Research
N2  - Background:
Irradiation with α-particles creates densely packed damage tracks along particle trajectories in exposed cells, including complex DNA damage and closely spaced double-strand breaks (DSBs) in hit nuclei. Here, we investigated the correlation of the absorbed dose to the blood and the number of α-induced DNA damage tracks elicited in human blood leukocytes after ex-vivo in-solution exposure with Ra-224. The aim was to compare the data to previously published data on Ra-223 and to investigate differences in DNA damage induction between the two radium isotopes.

Results:
Blood samples from three healthy volunteers were exposed ex-vivo to six different concentrations of Ra-224 dichloride. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the Ra-224 decay chain, ranging from 0 to 127 mGy. γ-H2AX + 53BP1 DNA damage co-staining and analysis was performed on ethanol-fixed leukocytes isolated from the irradiated blood samples. For damage quantification, α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci were enumerated in the exposed leukocytes. 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.

Conclusions:
Our data provide a first estimation of the DNA damage induced by Ra-224 in peripheral blood mononuclear cells. A comparison with our previously published Ra-223 data suggests that there is no difference in the induction of radiation-induced DNA damage between the two radium isotopes due to their similar decay properties.
KW  - 53BP1
KW  - DNA damage
KW  - γ-H2AX
KW  - biological dosimetry
KW  - absorbed dose to the blood
KW  - α-emitter
KW  - Ra-224
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176593
VL  - 8
IS  - 77
ER  -