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. 2022 Dec 1;198(6):599-614.
doi: 10.1667/RADE-22-00101.1.

Determination of Lethality Curve for Cobalt-60 Gamma-Radiation Source in Rhesus Macaques Using Subject-Based Supportive Care

Vijay K Singh  1   2 , Oluseyi O Fatanmi  1   2 , Stephen Y Wise  1   2 , Alana D Carpenter  1   2 , Cara H Olsen  3
Affiliations

Determination of Lethality Curve for Cobalt-60 Gamma-Radiation Source in Rhesus Macaques Using Subject-Based Supportive Care

Vijay K Singh et al. Radiat Res. .

Abstract

Well-characterized and validated animal models are required for the development of medical countermeasures (MCMs) for acute radiation syndrome to mitigate injury due to high doses of total- or partial-body irradiation. Animal models used in MCM development must reflect a radiation dose- and time-dependent relationship, clinical presentation, and pathogenesis of organ injuries in humans. The objective of the current study was to develop the lethality curve for the Armed Forces Radiobiology Research Institute high level cobalt-60 gamma-radiation source in nonhuman primates (NHPs) after total-body irradiation. A dose-response relationship was determined using NHPs (rhesus macaques, N = 36, N = 6/radiation dose) irradiated with 6 doses in the range of 6.0 to 8.5 Gy, with 0.5 Gy increments at a dose rate of 0.6 Gy/min. Animals were provided subject-based supportive care including blood transfusions and were monitored for 60 days postirradiation. Survival was the primary endpoint of the study and the secondary endpoint included hematopoietic recovery. The lethality curve suggested LD30/60, LD50/60, and LD70/60 values as 5.71, 6.78, and 7.84 Gy, respectively. The results of this study will be valuable to provide specific doses for various lethalities of 60Co-gamma radiation to test radiation countermeasures in rhesus macaques using subject-based supportive care including blood transfusion.

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Figures

FIG. 1.
FIG. 1.
Survival curve of irradiated NHPs. Thirty-six NHPs were divided into six groups and were exposed to either 6.0, 6.5, 7.0, 7.5, 8.0, or 8.5 Gy (bilateral simultaneous, 0.6 Gy/min) 60Co γ radiation. Survival was monitored for 60 days postirradiation.
FIG. 2.
FIG. 2.
Probit analysis of irradiated NHPs. Vertical reference lines indicate (A) LD30/60 =5.71 (95% CI 3.87 to 7.56), (B) LD50/60, = 6.78 (95% CI 5.82 to 7.74), and (C) LD70/60 = 7.84 (95% CI 6.74 to 8.95).
FIG. 3.
FIG. 3.
Effects of various radiation doses on CBCs: white blood cells, red blood cells, hemoglobin, hematocrit, platelets, and neutrophils in irradiated NHPs. The data for each time point is presented as the mean for animals exposed to each dose of radiation.
FIG. 4.
FIG. 4.
Effects of various doses of radiation on CBCs: absolute counts of lymphocytes, monocytes, eosinophils, basophils, and reticulocytes in irradiated NHPs. The data for each time point is presented as the mean for animals exposed to each radiation dose.
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