A PRECLINICAL RODENT MODEL OF RADIATION-INDUCED LUNG INJURY FOR MEDICAL COUNTERMEASURE SCREENING IN ACCORDANCE WITH THE FDA ANIMAL RULE
A PRECLINICAL RODENT MODEL OF RADIATION-INDUCED LUNG INJURY FOR MEDICAL COUNTERMEASURE SCREENING IN ACCORDANCE WITH THE FDA ANIMAL RULE
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DOI：
10.1097/hp.0b013e31826386ef
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发表时间：
2012-10-01
期刊：
影响因子：
2.2
通讯作者：
Vujaskovic, Zeljko
中科院分区：
文献类型：
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作者：
Jackson, Isabel L.;Xu, Puting;Vujaskovic, Zeljko
临床前鼠模型发展的目的是确定辐射诱导的肺损伤的啮齿动物模型的病理生理结果足以代表人口预期的肺反应。该目标是基于担心C57BL/6J菌株可能不是人类致命辐射肺损伤的最合适的临床前模型。在这项研究中，作者通过评估三种小鼠菌株的发病率（肺功能，组织病理学损害）与死亡率之间的关系来评估这一问题：C57BL/6J，CBA/J和C57L/J。这些不同的菌株在辐射诱导的肺损伤的潜伏期和表型表达中表现出不同。通过比较每个菌株对人肺反应的反应，建立了人类辐射诱导的肺损伤的适当动物模型。可以将C57L/J和CBA/J鼠模型中的观测值推送到人类肺部，以评估辐射的作用机制，以及未来的功效测试和批准属于美国食品和食物的“动物规则”的药物药物管理（FDA）（21 CFR部分314和601）。健康物理。 103（4）：463-473; 2012
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). Health Phys. 103(4):463-473;2012