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

Background: Cesium-137 (Cs-137) 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 Cs-137 radionuclide exposures on DNA damage in mouse blood and spleen mononuclear cells (MNCs) in vivo using the gamma-H2AX biomarker, and to develop a mathematical formalism for these processes. Results: C578L/6 mice were injected with a range of (CsCI)-Cs-137 activities (5.74, 6.66, 7.65 and 928 MBq) to achieve total-body committed doses of similar to 4 Gy at Days 3, 5, 7, and 14. Close to 50% of Cs-137 was excreted by day 5, leading to a slower rate of decay for the remaining time of the study; Cs-137 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 gamma-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 gamma-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 gamma-H2AX repair kinetics to develop a mathematical formalism, which can relatively accurately predict injected Cs-137 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 gamma-H2AX response after protracted exposures.