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γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90.

Turner HC, Shuryak I, Weber W, Doyle-Eisele M, Melo D, Guilmette R, Amundson SA, Brenner DJ - PLoS ONE (2015)

Bottom Line: 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 mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America.

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.

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Retention profiles for 137CsCl and 90SrCl2.
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pone.0143815.g001: Retention profiles for 137CsCl and 90SrCl2.

Mentions: Biokinetics and dosimetry measurements for both the radionuclides were calculated based on the whole-body retention data. Fig 1 shows the whole-body counting data normalized to the amount of 137Cs and 90Sr present in each animal on Day 0 following injection. Table 1 shows the accumulated total body absorbed doses (Gy) calculated at specific time points following isotope injection. The biokinetic and dosimetric modeling showed that within the first week, more than 60% of the initial (8.0 ± 0.3 MBq) 137Cs activity and 90Sr (low dose; 200 ± 0.3 kBq) have been excreted, whereas ~ 60% remained after injection with (high dose; 1.55 ± 0.1 MBq) 90Sr. By Day 30, 96% of 137Cs was excreted whereas 37% and 24% remained in the skeleton for 90Sr (high dose) and 90Sr (low dose), respectively. Table 1 also highlights the changing dose rates for the accumulation of the radionuclides over the 30-day study time. The results show that the dose rate is more or less proportional to the administered isotope activity. For 137Cs, the dose rate decreased with increasing elimination from the body. The approximate average dose rate of accumulation between Day 3 and Day 5 was 0.52 mGy/min whereas between Day 5 and 20 the average dose rate had dropped by ~50% to 0.25 mGy/min leading to a further 90% drop by Day 30. For high-dose 90Sr, the accumulation rate increased up to Day 9, after which time there was an approximate 60% drop in the rate by Day 23 with no further accumulation by Day 30. In contrast, for low-dose 90Sr, there was no apparent decrease in the dose rate between Day 7 and Day 25.


γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90.

Turner HC, Shuryak I, Weber W, Doyle-Eisele M, Melo D, Guilmette R, Amundson SA, Brenner DJ - PLoS ONE (2015)

Retention profiles for 137CsCl and 90SrCl2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664397&req=5

pone.0143815.g001: Retention profiles for 137CsCl and 90SrCl2.
Mentions: Biokinetics and dosimetry measurements for both the radionuclides were calculated based on the whole-body retention data. Fig 1 shows the whole-body counting data normalized to the amount of 137Cs and 90Sr present in each animal on Day 0 following injection. Table 1 shows the accumulated total body absorbed doses (Gy) calculated at specific time points following isotope injection. The biokinetic and dosimetric modeling showed that within the first week, more than 60% of the initial (8.0 ± 0.3 MBq) 137Cs activity and 90Sr (low dose; 200 ± 0.3 kBq) have been excreted, whereas ~ 60% remained after injection with (high dose; 1.55 ± 0.1 MBq) 90Sr. By Day 30, 96% of 137Cs was excreted whereas 37% and 24% remained in the skeleton for 90Sr (high dose) and 90Sr (low dose), respectively. Table 1 also highlights the changing dose rates for the accumulation of the radionuclides over the 30-day study time. The results show that the dose rate is more or less proportional to the administered isotope activity. For 137Cs, the dose rate decreased with increasing elimination from the body. The approximate average dose rate of accumulation between Day 3 and Day 5 was 0.52 mGy/min whereas between Day 5 and 20 the average dose rate had dropped by ~50% to 0.25 mGy/min leading to a further 90% drop by Day 30. For high-dose 90Sr, the accumulation rate increased up to Day 9, after which time there was an approximate 60% drop in the rate by Day 23 with no further accumulation by Day 30. In contrast, for low-dose 90Sr, there was no apparent decrease in the dose rate between Day 7 and Day 25.

Bottom Line: 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 mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America.

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.

Show MeSH
Related in: MedlinePlus