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Developing and Comparing Models of Hematopoietic-Acute Radiation Syndrome in Göttingen and Sinclair Minipigs
International Journal of Radiation Biology ( IF 2.1 ) Pub Date : 2020-09-10
Melanie Doyle-Eisele, Jeremy Brower, Kenneth Aiello, Emily Ferranti, Michael Yaeger, Guodong Wu, Waylon Weber

Purpose: Current animal models of hematopoietic-acute radiation syndrome (H-ARS) are resource intensive and have limited translation to humans, thereby inhibiting the development of effective medical countermeasures (MCM)s for radiation exposure.

Materials and Methods: To improve the MCM pipeline, we developed models of H-ARS in male Göttingen and Sinclair minipigs. Weight matched Göttingens and Sinclairs received total body irradiation (TBI; 1.50 – 2.10 Gy and 1.94 – 2.90 Gy respectively), were observed for up to 45 days with blood collections for clinical pathology analysis, and were examined during gross necropsy.

Results: The lethal dose for 50% of the population over the course of 45 days (LD50/45) with “field” supportive care (primarily antibiotics and hydration support) and implanted vascular access ports was 1.89 and 2.53 Gy for Göttingens and Sinclairs, respectively. Both minipig strains exhibited prototypical H-ARS characteristics, experiencing thrombocytopenia and neutropenia, and nadirs approximately 14 days following irradiation, slightly varying with dose. Both strains experienced increased bruising, petechia, and signs of internal hemorrhage in the lungs, GI, heart, and skin. All observations were noted to correlate with dose more closely in Sinclairs than in Göttingens.

Conclusion: The results of this study provide a template for future MCM development in an alternate species, and support further development of the Göttingen and Sinclair minipig H-ARS models.



中文翻译:

哥廷根和辛克莱迷你猪的造血-急性放射综合症模型的开发和比较

目的:当前的造血-急性放射综合症(H-ARS)动物模型需要大量资源,并且对人类的翻译有限,从而抑制了有效的放射治疗医学对策(MCM)的发展。

材料和方法:为了改善MCM管道,我们开发了雄性哥廷根和辛克莱小型猪的H-ARS模型。体重匹配的哥廷根人和辛克莱人接受了全身照射(分别为TBI; 1.50 – 2.10 Gy和1.94 – 2.90 Gy),观察了长达45天的血液并进行了临床病理分析,并在尸检时进行了检查。

结果:在45天的过程中(LD 50/45),采用“现场”支持治疗(主要是抗生素和水化支持)并植入血管通路的致死剂量为1.89和2.53 Gy(对于Göttingens和Sinclairs) , 分别。两种小型猪菌株均表现出原型H-ARS特征,经历了血小板减少和中性粒细胞减少,辐射后约14天出现最低点,随剂量而略有变化。两种菌株都经历了瘀伤,瘀斑和肺,胃肠道,心脏和皮肤内出血的迹象。注意到所有的观察结果与辛格莱斯的剂量比在哥廷根的剂量更紧密相关。

结论:这项研究的结果为未来MCM在其他物种中的发展提供了模板,并支持Göttingen和Sinclair minipig H-ARS模型的进一步发展。

更新日期:2020-09-10
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