The major burden of radiation injury among survivors lies in long-term effects, including organ failure, fibrosis, and neoplasia. The Survivor Cohort of the Radiation Countermeasures Center of Research Excellence will build upon current long-term data acquired from irreplaceable cohorts of previously irradiated nonhuman primates (NHP), followed for up to 8 years after irradiation. These NHP have been collected from investigators at the Armed Forces Radiobiology Research Institute (AFRRI), the primate studies group at the University of Maryland (UMD), the University of Chicago (UIC), from DARPA NHP trials (Harvard/Lovelace Respiratory Research Institute), and other populations. Animals acquired to date have been exposed to single whole body doses of ionizing radiation in the range of 2 to 8.4 Gy, with the most valuable animals exposed in the higher dose range of 6.5-8.4 Gy. We have also acquired age-matched non-irradiated animals to serve as controls. Observations include clinical examinations, imaging (CT and MRI scans), hematology, clinical chemistry, and necropsy/histopathology. Major areas of focus include: ? Bone Marrow: Gene expression array and cytogenetic biomarker studies to monitor hematopoietic and immune recovery, and potential carcinogenic changes in bone marrow. Exome sequencing to date indicates a variety of either acquired or adaptive/selective mutations in DNA repair pathways, with potential functional relevance. ? Immune Recovery: Measures of thymopoiesis, immune recovery, and vaccine response; findings to date indicate chronic depletion of regulatory T cells and restriction of the antibody response repertoire. ? Cardiovascular System: Assessment of radiation-induced cardiovascular changes, including lipid profiles, ultrasound studies, and pathologic assessments of atherosclerosis and myocardial fibrosis (to date observed in half of all irradiated animals at necropsy). ? Kidney: Radiation-induced renal pathology, including clinical pathology monitoring and imaging studies; higher-dose animals show impairment of renal function. ? Brain: Radiation-induced brain injury and cognitive impairment, including computed tomography and magnetic resonance imaging, and training of animals for cognitive testing. Lower gray matter volume is currently evident in irradiated animals. ? Gastrointestinal Tract: Radiation-induced chronic intestinal injury assessed by endoscopy, biopsy/histopathology, and malabsorption studies; effects currently are not profound. ? Lung: Pulmonary injury (pneumonitis and fibrosis) assessed by clinical, imaging, and pathology studies. To date we have seen chronic pulmonary disease including pulmonary fibrosis, bronchopulmonary epithelial hyperplasia and dysplasia. ? In addition, unexpected patterns of radiation-associated disease have emerged in our current long-term cohort, including type 2 diabetes mellitus, osteopenia, and neoplasia.
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