Postmortem Findings from the Wake Forest University Radiation Late Effects Cohort of Rhesus Monkeys (Macaca mulatta)

The Wake Forest Radiation Late Effects Cohort (RLEC), formerly known as the Radiation Survivors Cohort, of rhesus (Macaca mulatta) non-human primates (NHPs) is a unique colony of long-term survivors of total-body irradiation (TBI). The cohort includes 212 live animals, with 17% being unirradiated controls, and 104 deceased animals, including 15% controls. This cohort has been monitored for over 16 years, with an average observation period of 5 years. Irradiated NHPs were exposed to single TBI doses ranging from 1.14 to 8.5 Gy (average = 6.1 Gy). One animal received 10 Gy partial-body irradiation with approximately 5% bone marrow sparing. In this paper, we present the postmortem findings from 104 deceased members of the RLEC. Animals underwent a comprehensive, standardized necropsy, which included a complete gross and histopathologic examination of 36 organs and tissues. For this study, necropsy reports of 104 deceased animals (87 irradiated and 17 controls) were reviewed by two board-certified veterinary pathologists (GWS and JMC), and all diagnoses were cataloged. A total of 2,790 diagnoses were recorded across all organ systems and analyzed for statistical differences between irradiated and control animals using Fisher's exact test. Deceased control animals ranged in age from 9.9 to 21.4 years (mean = 16 years), whereas irradiated animals were younger, with ages from 2.7 to 23.1 years (mean = 11.6 years, P = 0.0001). The time from irradiation to death ranged from 0.3 to 14.4 years (average = 6.4 years). Radiation doses for these deceased animals ranged from 3.5 to 8.5 Gy (average = 6.6 Gy). The prevalence of most lesions was not statistically different from controls. Common findings among the irradiated animals included multi-organ fibrosis and chronic inflammation. Additionally, there was an increased occurrence of neoplasia in the irradiated animals. These data represent comprehensive, systemic, long-term pathology assessments conducted on a large group of NHPs years after total-body irradiation in the molecular era. They provide a solid foundation for molecular and translational studies of radiation late effects. The fact that many of the same lesions appeared in both the irradiated and unirradiated control animals, despite the significant age difference, suggests an accelerated-aging phenotype in the survivors.