Faculty Collaboration Database

WAG/RijCmcr rat models for injuries to multiple organs by single high dose ionizing radiation: similarities to nonhuman primates (NHP). Int J Radiat Biol 2020 Jan;96(1):81-92

Date

12/24/2018

Pubmed ID

30575429

DOI

10.1080/09553002.2018.1554921

Scopus ID

2-s2.0-85060053811 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

Purpose: Defined animal models are needed to pursue the FDA Animal Rule for approval of medical countermeasure for radiation injuries. This study compares WAG/RijCmcr rat and nonhuman primate (NHP) models for acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE).Materials and methods: Irradiation models include total body irradiation, partial body irradiation with bone marrow sparing and whole thorax lung irradiations. Organ-specific sequelae of radiation injuries were compared using dose-response relationships.Results and conclusions: Rats and NHP manifest similar organ dysfunctions after radiation, starting with acute gastrointestinal (GI-ARS) and hematopoietic (H-ARS) syndromes followed by lung, heart and kidney toxicities. Humans also manifest these sequelae. Latencies for injury were earlier in rats than in NHP. After whole thorax lung irradiations (WTLI) up to 13 Gy, there was recovery of lung function from pneumonitis in rats. This has not been evaluated in NHP. The latency, incidence, severity and progression of radiation pneumonitis was not influenced by early multi-organ injury from ARS in rats or NHP. Rats developed more severe radiation nephropathy than NHP, and also progressed more rapidly. Dosimetry, anesthesia, environment, supportive care, euthanasia criteria etc., may account for the alterations in radiation sensitivity observed between species.

Author List

Fish BL, MacVittie TJ, Szabo A, Moulder JE, Medhora M

Author

Aniko Szabo PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Radiation Syndrome
Animals
Disease Models, Animal
Dose-Response Relationship, Radiation
Female
Hematopoiesis
Humans
Macaca mulatta
Male
Radiation Pneumonitis
Rats
Whole-Body Irradiation