Abstract/Summary
Acute effects of radiation exposures are the focus of emergency medical responses and mitigation efforts, but
the major burden of radiation injury lies in delayed effects. These late and usually long-term effects of exposure
on normal healthy tissues include cellular, molecular, and metabolic changes leading to organ dysfunction and
failure; fibrosis; and neoplasia. The Radiation Survivor Cohort (RSC) is a unique and irreplaceable
population of nonhuman primate (NHP) radiation survivors, which serves the nation’s need to identify and
understand the late effects of radiation exposure; provides long-term outcome validation of acute biomarker
measurements; and provides critical data regarding tissue damage and recovery. RSC investigators at Wake
Forest have assessed adverse effects of single-dose whole-body exposures of 1-8.5 Gy in over 140 rhesus
monkeys observed for up to 15 years after irradiation, with 38 controls. The cohort includes juvenile and adult
exposures, males and females, and subsets of animals that did or did not receive mitigating treatments such
as hematopoietic growth factors or antibiotics. Observations have included an annual cycle of clinical
examinations, imaging (ultrasound, CT and MRI), clinical pathology, and ultimately necropsy examinations.
Major diseases identified to date include (1) metabolic disease and type II diabetes mellitus; (2) myocardial
diastolic dysfunction with fibrosis; (3) neurologic disorders with MRI-detected brain lesions; (4) chronic renal
disease with fibrosis; (5) gastrointestinal disease resulting in chronic diarrhea; (6) immune compromise with
impaired response repertoire; (7) neoplasms, primarily including sarcomas, hematopoietic, epithelial, and
neuroendocrine types. Other stereotypical radiation effects are seen, such as cataracts and gonadal atrophy at
higher doses. Multiple disorders in the same animal were common, up to 8 in high-dose animals, with diabetes
being the most common co-morbid condition. The overarching goal for the proposed new funding period is to
identify and study relevant patterns of post-irradiation morbidity and mortality in this unique, controlled, well-
defined NHP population, by collaborating and sharing data with NIH-funded and other federally-funded
investigators. Sharing will include samples (blood, tissue, body fluids, microbiome) and data (clinical, imaging,
pathology, gene sequence, gene expression, immunophenotyping and other data types) with an active
investigator community currently consisting of 62 investigators across 18 institutions, including outreach to new
investigative teams. The specific aims of this program are to (1) identify and share patterns of post-irradiation
morbidity; (2) identify genomic and biomarker characteristics of animals with differing radiation-induced
disorders; (3) assess late effects of prior mitigator treatment; and (4) refine the cohort to balance age, sex,
dose, and mitigator type, in order to maximize the scope of inference of data derived from the cohort.