Developing and comparing models of hematopoietic-acute radiation syndrome in Göttingen and Sinclair minipigs

Abstract

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.