Abstract
In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis.
Highlights
In the event of an accidental or terrorist incident, the release of radionuclides to the environment is a major concern for acute and chronic exposures
Increased information on radiation doses and risk to human health comes from studies on populations exposed to external radiation, while quantitative estimates of the radiotoxicity of internal emitters in humans is limited to a few radionuclides [1]
The results show that at Day 5 the γ-H2AX yields are significantly above non-irradiated baseline levels, the fact that there are no blood draws between Day 5 and Day 20 makes it difficult to determine at what the point the γ-H2AX yields continue to decrease or when they start to increase
Summary
In the event of an accidental or terrorist incident, the release of radionuclides to the environment is a major concern for acute and chronic exposures. Increased information on radiation doses and risk to human health comes from studies on populations exposed to external radiation, while quantitative estimates of the radiotoxicity of internal emitters in humans is limited to a few radionuclides [1]. Radioactive isotopes of Cesium-137 (137Cs) and Strontium-90 (90Sr) are considered to be some of the most dangerous radionuclides released into the environment in terms of their high radioactivity, long-lived effects (physical half-lives of about 30 years) and the ease in which they are taken up into the food chain [1,2,3]. Radionuclide waste contamination of the Techa River by the Mayak nuclear weapons facility in the South Urals exposed thousands of people living in rural villages along the river to protracted internal and external exposures to ionizing radiation [6]. The 137Cs-based radiological accident at the city of Goiânia in central Brazil illustrates the catastrophic effects of large scale environmental radioactive contamination from a loss of control of a radiotherapy source (housing about 100 g CsCl2) stolen from an abandoned hospital site radioactive contamination [10]
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