Article ; Online: Delayed effects of radiation exposure in a C57L/J mouse model of partial body irradiation with ~2.5% bone marrow shielding.
2024 Volume 12, Page(s) 1349552
Abstract: ... The C57L/J mouse model of partial body irradiation (PBI) with 2.5% bone marrow shielding (BM2.5) is being ... the dose response relationship and progression of radiation injury in the C57L/J mouse and to evaluate its suitability for use ... female C57L/J mice were exposed to PBI BM2.5 with one hindlimb shielded from radiation, representing ~2.5 ...
| Abstract | Introduction: Mouse models of radiation injury are critical to the development of medical countermeasures (MCMs) against radiation. Now that MCMs against hematopoietic acute radiation syndrome (H-ARS) have achieved regulatory approval, attention is shifting to develop MCMs against the adverse effects of gastrointestinal acute radiation syndrome (GI-ARS) and delayed effects of acute radiation exposure (DEARE). The C57L/J mouse model of partial body irradiation (PBI) with 2.5% bone marrow shielding (BM2.5) is being leveraged to examine both GI-ARS and DEARE effects. Within days of PBI, mice may develop H- and GI-ARS followed several months later by DEARE as a multi-organ injury, which typically involves the lung and kidney (L- and K-DEARE, respectively). The objective of this manuscript is to describe the dose response relationship and progression of radiation injury in the C57L/J mouse and to evaluate its suitability for use in DEARE MCM testing. Materials and methods: In two separate studies conducted over 2 years, male and female C57L/J mice were exposed to PBI BM2.5 with one hindlimb shielded from radiation, representing ~2.5% bone marrow shielding/sparing. Mice were X-ray irradiated at doses ranging from 9 to 13 Gy at 10 to 12 weeks of age for the purposes of assessing ARS survival at 30 days and DEARE survival at 182 days post-irradiation. Clinical indicators of ARS and DEARE were determined by clinical observations, body weights, hematology, clinical chemistry, magnetic resonance imaging (MRI) of lung, and histopathology of selected tissues. Results: C57L/J mice developed canonical ARS responses of hematopoietic atrophy and gastrointestinal injury resulting in dose dependent mortality at doses ≥11 Gy between 1- and 15-days post-irradiation. In animals that survived ARS, DEARE associated mortality occurred in dose dependent fashion at ≥9 Gy for both sexes between 60- and 159-days post-irradiation with histopathology examinations indicating lung injury as the primary cause of death in moribund animals. Conclusion: The PBI BM2.5 C57L/J mouse model reliably produced known H- and GI-ARS effects at doses greater than those resulting in DEARE effects. Because of this, the C57L/J mouse can be used to test MCMs against L-DEARE injury, while avoiding ARS associated mortality. |
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| MeSH term(s) | Male ; Female ; Mice ; Animals ; Bone Marrow/pathology ; Bone Marrow/radiation effects ; Acute Radiation Syndrome/etiology ; Acute Radiation Syndrome/pathology ; Disease Models, Animal ; Lung/pathology |
| Language | English |
| Publishing date | 2024-03-12 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 2711781-9 |
| ISSN | 2296-2565 ; 2296-2565 |
| ISSN (online) | 2296-2565 |
| ISSN | 2296-2565 |
| DOI | 10.3389/fpubh.2024.1349552 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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