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 (LD_50/45) 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.

Keywords:

• Acute radiation syndrome (ARS)
• miniswine
• lethality
• total body irradiation (TBI)

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported in part or wholly by funds from the Biomedical Advanced Research and Development Authority, Department of Health and Human Services, under Contract no. HHSO100200100004I and Task order no. HHSO10033001T. The authors acknowledge the continuous discussion, insight, and constructive critique of colleagues at BARDA.

Notes on contributors

Melanie Doyle-Eisele

Melanie Doyle-Eisele, PhD, is the Director of Life Sciences and Senior Scientist at Lovelace Biomedical, Albuquerque, NM.

Jeremy Brower

Jeremy Brower, PhD, is an Associate Research Scientist and Study Director at Lovelace Biomedical, Albuquerque, NM.

Kenneth Aiello

Kenneth Aiello is a Research Associate at Lovelace Biomedical, Albuquerque, NM.

Emily Ferranti

Emily Ferranti is a Research Associate at Lovelace Biomedical, Albuquerque, NM.

Michael Yaeger

Michael Yaeger is a Research Associate at Lovelace Biomedical, Albuquerque, NM.

Guodong Wu

Guodong Wu is an Associate Research Scientist and Statistician at Lovelace Biomedical, Albuquerque, NM.

Waylon Weber

Waylon Weber PhD is a Senior Scientist and Study Director at Lovelace Biomedical, Albuquerque, NM.