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A Further Comparison of Pathologies after Thoracic Irradiation among Different Mouse Strains: Finding the Best Preclinical Model for Evaluating Therapies Directed Against Radiation-Induced Lung Damage

The human lung is among the most sensitive and critical tissues of concern in localized and systemic radiation exposures, and it is a subject of active preclinical research for evaluating mitigating therapies within the radiation countermeasures program. Our previous study comparing C57BL/6, CBA and...

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Published in:Radiation research 2011-04, Vol.175 (4), p.510-518
Main Authors: Jackson, Isabel L, Vujaskovic, Zeljko, Down, Julian D
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description The human lung is among the most sensitive and critical tissues of concern in localized and systemic radiation exposures, and it is a subject of active preclinical research for evaluating mitigating therapies within the radiation countermeasures program. Our previous study comparing C57BL/6, CBA and C57L mice after whole-thorax irradiation pointed to the problems of late pleural effusions that prevented the full development of lung injury in C57BL/6 mice and suggested that the CBA and C57L strains are more favorable for modeling lung injury in humans (Jackson et al., Radiat. Res.173, 10–20, 2010). We extended these comparisons to include three other mouse strains (BALB/c, C57BR/J and A/J mice) irradiated with 10, 12.5 or 15 Gy. Most of these mice were unable to survive the first 6 months and presented with a mixture of lung injury and pleural effusions as determined from gross pathology, histology and micro-CT. The independent and varying development of compressive pleural effusions of ill-defined etiology represents a concern for these strains in that they may not satisfy the preclinical requirements for approval of medical countermeasures (e.g. radiation mitigators) for human use. Thus, among the various different mouse strains studied so far for these pathologies, only three (CBA, C3H and C57L) appear to be desirable in exhibiting an early wave of pulmonary dysfunction attributed exclusively to radiation pneumonitis and for further assessment of radioprotective and mitigating therapies. C57L mice are particularly relevant in that they show significant lung damage at lower radiation doses that are closer to what is predicted for humans.
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subjects Animals
Disease Models, Animal
Fibrosis
Humans
Irradiation
Lung Diseases - etiology
Lung Diseases - physiopathology
Lung Diseases - therapy
Lungs
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Pathology
Pleural effusion
Pneumonia
Radiation damage
Radiation Dosage
Radiation Injuries - etiology
Radiation Injuries - physiopathology
Radiation Injuries - therapy
Radiation pneumonitis
Radiotherapy
REGULAR ARTICLES
Species Specificity
Thorax - radiation effects
title A Further Comparison of Pathologies after Thoracic Irradiation among Different Mouse Strains: Finding the Best Preclinical Model for Evaluating Therapies Directed Against Radiation-Induced Lung Damage
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