The progression of radiation injury in a Wistar rat model of partial body irradiation with ∼5% bone marrow shielding. 2023

Tyler Beach, and James Bakke, and Ed Riccio, and Harold S Javitz, and Denise Nishita, and Shweta Kapur, and Deborah I Bunin, and Polly Y Chang
SRI International, Menlo Park, CA, USA.

To describe the dose response relationship and natural history of radiation injury in the Wistar rat and its suitability for use in medical countermeasures (MCM) testing. In two separate studies, male and female rats were exposed to partial body irradiation (PBI) with 5% bone marrow sparing. Animals were X-ray irradiated from 7 to 12 Gy at 7-10 weeks of age. Acute radiation syndrome (ARS) survival at 30 days and delayed effects of acute radiation exposure (DEARE) survival at 182 days were assessed. Radiation effects were determined by clinical observations, body weights, hematology, clinical chemistry, magnetic resonance imaging of lung, whole-body plethysmography, and histopathology. Rats developed canonical ARS responses of hematopoietic atrophy and gastrointestinal injury resulting in mortality at doses ≥8Gy in males and ≥8.5 Gy in females. DEARE mortality occurred at doses ≥8Gy for both sexes. Findings indicate lung, kidney, and/or liver injury, and persistent hematological dysregulation, revealing multi-organ injury as a DEARE. The Wistar rat PBI model is suitable for testing MCMs against hematopoietic and gastrointestinal ARS. DEARE multi-organ injury occurred in both sexes irradiated with 8-9Gy, also suggesting suitability for polypharmacy studies addressing the combination of ARS and DEARE injury.

UI MeSH Term Description Entries
D008297 Male Males
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D005260 Female Females
D006413 Hematopoietic System The blood-making organs and tissues, principally the bone marrow and lymph nodes. Hematopoietic Systems,System, Hematopoietic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D041981 Gastrointestinal Tract Generally refers to the digestive structures stretching from the MOUTH to ANUS, but does not include the accessory glandular organs (LIVER; BILIARY TRACT; PANCREAS). Digestive Tract,GI Tract,Digestive Tracts,GI Tracts,Gastrointestinal Tracts
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D054508 Acute Radiation Syndrome A condition caused by a brief whole body exposure to more than one sievert dose equivalent of radiation. Acute radiation syndrome is initially characterized by ANOREXIA; NAUSEA; VOMITING; but can progress to hematological, gastrointestinal, neurological, pulmonary, and other major organ dysfunction. Acute Radiation Syndromes,Radiation Syndrome, Acute,Radiation Syndromes, Acute

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