A preclinical rodent model of radiation-induced lung injury for medical countermeasure screening in accordance with the FDA animal rule

Isabel L. Jackson, Puting Xu, Caroline Hadley, Barry P. Katz, Ross McGurk, Julian D. Down, Zeljko Vujaskovic

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)463-473
Number of pages11
JournalHealth physics
Volume103
Issue number4
DOIs
StatePublished - Oct 1 2012

Keywords

  • lungs rodent
  • modeling dose assessment
  • radiation damage
  • radiation medical

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis
  • Epidemiology

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