Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Radiat Res. 2022 Dec 1;198(6):599-614. doi: 10.1667/RADE-22-00101.1.
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.
需要具有明确特征和经过验证的动物模型来开发用于治疗急性辐射综合征的医疗对策(MCM),以减轻全身或部分身体照射引起的伤害。用于 MCM 开发的动物模型必须反映出剂量和时间依赖性关系、临床表现以及人类器官损伤的发病机制。本研究的目的是在非人类灵长类动物(NHP)中开发武装部队放射生物学研究所高剂量钴-60 伽马辐射源的致死曲线,这些 NHP 经过全身照射。使用剂量范围为 6.0 至 8.5 Gy 的 6 个剂量照射 NHP(恒河猴,N = 36,N = 6/辐射剂量),剂量率为 0.6 Gy/min,剂量递增 0.5 Gy。为动物提供基于个体的支持性护理,包括输血,并在照射后 60 天进行监测。生存是本研究的主要终点,次要终点包括造血恢复。致死曲线表明 LD30/60、LD50/60 和 LD70/60 值分别为 5.71、6.78 和 7.84 Gy。这项研究的结果将有助于提供各种 60Co-γ射线的致死剂量,以便在恒河猴中使用基于个体的支持性护理(包括输血)测试辐射对策。