A Preclinical Rodent Model of Radiation-induced Lung Injury for Medical Countermeasure Screening in Accordance With the FDA Animal Rule

Division of Translational Radiation Sciences, Dept of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Health physics (Impact Factor: 1.27). 10/2012; 103(4):463-73. DOI: 10.1097/HP.0b013e31826386ef
Source: PubMed


The purpose of preclinical murine model development is to establish that the pathophysiological outcome of the rodent model of radiation-induced lung injury is sufficiently representative of the anticipated pulmonary response in the human population. This objective is based on concerns that the C57BL/6J strain may not be the most appropriate preclinical model of lethal radiation lung injury in humans. In this study, the authors assessed this issue by evaluating the relationship between morbidity (pulmonary function, histopathologic damage) and mortality among three strains of mice: C57BL/6J, CBA/J, and C57L/J. These different strains display variations in latency and phenotypic expression of radiation-induced lung damage. By comparing the response of each strain to the human pulmonary response, an appropriate animal model(s) of human radiation-induced pulmonary injury was established. Observations in the C57L/J and CBA/J murine models can be extrapolated to the human lung for evaluation of the mechanisms of action of radiation as well as future efficacy testing and approving agents that fall under the "Animal Rule" of the U.S. Food and Drug Administration (FDA) (21 CFR Parts 314 and 601).

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    • "The MCART database. MCART maximizes prospective experimental design through use of its extensive database and well-characterized and validated animal models in the mouse and NHP (Farese et al. 2009; MacVittie et al. 2012a and b; Booth et al. 2012a and b; Plett et al. 2012, 2014; Chua et al. 2012, 2014; Jackson et al. 2012; Garofalo et al. 2014; MacVittie et al. 2014). MCART recently focused its animal model research platform to include procurement of signs and laboratory parameters of multiorgan damage at all available observation times through the appearance of the ARS and DEARE. "
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    • "It is important to understand and elucidate the mechanisms that underlie radiation-induced fibrosis (RIF). Many animal models have been established to study RIF in multiple organs, such as lung (Jackson et al. 2012), GI (Rieder et al. 2012), and liver (Du et al. 2010). Until recently, these RIF models were established primarily using rodents. "
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    • "One of MCART's functions is to develop/characterize animal models of radiation injury. Accordingly, MCART has had success establishing total body irradiation doseresponse ranges and survival curves for H-ARS and GI-ARS in mice and in lung whole-thorax irradiation [Booth et al., 2012a; Jackson et al., 2012; McGurk et al., 2012; Plett et al., 2012] "
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