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Selecting the Most Relevant Mouse Strains for Evaluating Radiation-Induced Multiple Tissue Injury after Leg-Shielded
Julian D Down1, Milton R Cornwall-Brady1, Wei Huang1
1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Radiation Research
|July 27, 2024
Summary
A new partial-body irradiation (PBI) mouse model using cesium-137 gamma rays simulates radiological incidents. This model aids in developing medical countermeasures for radiation injuries, identifying specific mouse strains for different injury types.
Area of Science:
- Radiation Biology
- Medical Countermeasures
- Animal Models
Background:
- Need for animal models simulating inhomogeneous radiation exposure post-radiological incidents.
- Requirement for platforms to develop medical countermeasures.
- Existing models lack sufficient simulation of large-scale, inhomogeneous exposures.
Purpose of the Study:
- To develop and assess a partial-body irradiation (PBI) mouse model using 137Cs gamma rays with hind limb shielding.
- To evaluate the sequelae of radiation injuries to the gastrointestinal tract, bone marrow, and lung.
- To compare responses across different mouse strains (C57BL/6J, C57L/J, CBA/J, FVB/NJ).
Main Methods:
- Developed a PBI model with hind limb (tibia) shielding using 137Cs gamma rays.
- Administered PBI to unanesthetized mice.
- Assessed acute and delayed radiation syndromes, including body weight loss, peripheral blood cell counts, and pulmonary injury via micro-CT and histology.
Main Results:
- Marginal bone marrow shielding (∼2%) provided protection against lethality and allowed dose escalation.
- C57BL/6J mice showed highest sensitivity to radiation-induced body weight loss (enteritis).
- C57L/J mice developed lethal latent pulmonary injury (pneumonitis) at 12 Gy, comparable to other models and human predictions.
- C57BL/6 mice at 14 Gy exhibited pleural effusions, an anomaly noted in previous studies.
Conclusions:
- The developed PBI model effectively simulates radiological incidents with high-energy photons.
- C57BL/6J mice are suitable for studying early gastrointestinal and hematological syndromes.
- C57L/J mice are optimal for investigating delayed pulmonary effects of acute radiation exposure, relevant to human disease.
