Issa Melendez-Miranda, Oluseyi O Fatanmi, Stephen Y Wise, Sarah A Petrus, Alana D Carpenter, Cara Olsen, Artur A Serebrenik, Luis A Lugo-Roman, Thomas M Seed, Michael D Kaytor, Vijay K Singh
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引用次数: 0
摘要
为了制定辐射医学对策,以减轻因急性暴露于高剂量全身或局部辐射而造成的损伤,需要具有良好特征的急性辐射综合征动物模型。这样的动物模型必须揭示辐射剂量和时间依赖关系,损伤的发病机制和临床表现类似于人类。本研究的重点是调查食蟹猴急性暴露于相对高剂量全身辐射的临床反应,主要是致死模式。由于猕猴的优势和首选亚种恒河猴的供应有限,以及它们在其他高优先领域的使用有限,因此目前进行此类调查是有意义的。本研究以食蟹猕猴为研究对象,在0.6 Gy/min的剂量率下,采用3种不同的辐射剂量(4.7、5.8和6.5 Gy, N = 24、N = 8/辐射剂量),初步确定了食蟹猕猴的剂量-反应关系。为动物提供基于受试者的支持治疗,不包括血液制品,并监测放射后60天的生存情况,这是主要终点,次要终点是造血恢复。致死曲线显示LD30/60、LD50/60和LD70/60分别为4.8、5.3和5.8 Gy。这项研究的初步结果被认为对未来评估新开发的利用猕猴替代亚种即食蟹猕猴(Macaca fascicularis)治疗急性辐射损伤的医疗对策的功效至关重要。
Lethality Assessments for Acutely Irradiated Cynomolgus Macaques Under Subject-based Care.
Well-characterized animal models of acute radiation syndrome are needed for the development of radiation medical countermeasures to mitigate injury due to acute exposure to high doses of total- or partial-body radiation. Such animal models must reveal a radiation dose- and time-dependent relationship, pathogenesis of injury, and clinical presentation similar to humans. The focus of this study was to investigate clinical responses, principally lethality patterns, of cynomolgus macaques acutely exposed to relatively high doses of total-body radiation. Such investigations are currently relevant due to the limited availability of rhesus macaques, the dominant and preferred macaque subspecies, due to limited supply and their use in other high-priority areas. In this study employing cynomolgus macaques, a preliminary dose-response relationship was determined using three different radiation doses (4.7, 5.8 and 6.5 Gy, n = 24, n = 8/radiation dose) at a dose rate of 0.6 Gy/min. Animals were provided subject-based supportive care excluding blood products and were monitored for 60 days postirradiation for survival, which was the primary endpoint and the secondary endpoint was hematopoietic recovery. The lethality curve suggested LD30/60, LD50/60, and LD70/60 values as 4.8, 5.3, and 5.8 Gy, respectively. The initial results of this study are deemed critical for future efficacy assessments of newly developed medical countermeasures for acute radiation injuries by making use of an alternative subspecies of macaques, namely cynomolgus macaques (Macaca fascicularis).
期刊介绍:
Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology
and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically
ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or
biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with
chemical agents contributing to the understanding of radiation effects.