2019 Articles

Effect of dose and dose rate on temporal γ-H2AX kinetics in mouse blood and spleen mononuclear cells in vivo following Cesium-137 administration

Turner, Helen C.; Lee, Younghyun; Weber, Waylon; Melo, Dunstana; Kowell, Aimee; Ghandhi, Shanaz A.; Amundson, Sally A.; Brenner, David J.; Shuryak, Igor

Background
Cesium-137 (137Cs) is one of the major and most clinically relevant radionuclides of concern in a radiological dispersal device, “dirty bomb” scenario as well as in nuclear accidents and detonations. In this exposure scenario, a significant amount of soluble radionuclide(s) may be dispersed into the atmosphere as a component of fallout. The objectives of the present study were to investigate the effect of protracted 137Cs radionuclide exposures on DNA damage in mouse blood and spleen mononuclear cells (MNCs) in vivo using the γ-H2AX biomarker, and to develop a mathematical formalism for these processes.


Results
C57BL/6 mice were injected with a range of 137CsCl activities (5.74, 6.66, 7.65 and 9.28 MBq) to achieve total-body committed doses of ~ 4 Gy at Days 3, 5, 7, and 14. Close to 50% of 137Cs was excreted by day 5, leading to a slower rate of decay for the remaining time of the study; 137Cs excretion kinetics were independent of activity level within the tested range, and the absorbed radiation dose was determined by injected activity and time after injection. Measurements of γ-H2AX fluorescence in blood and spleen MNCs at each time point were used to develop a new biodosimetric mathematical formalism to estimate injected activity based on γ-H2AX fluorescence and time after injection. The formalism performed reasonably well on blood data at 2–5 days after injection: Pearson and Spearman’s correlation coefficients between actual and predicted activity values were 0.857 (p = 0.00659) and 0.929 (p = 0.00223), respectively.


Conclusions
Despite the complicated nature of the studied biological system and the time-dependent changes in radiation dose and dose rate due to radionuclide excretion and other processes, we have used the γ-H2AX repair kinetics to develop a mathematical formalism, which can relatively accurately predict injected 137Cs activity 2–5 days after initial exposure. To determine the assay’s usefulness to predict retrospective absorbed dose for medical triage, further studies are required to validate the sensitivity and accuracy of the γ-H2AX response after protracted exposures.