title: A preclinical rodent model of radiation-induced lung injury for medical countermeasure screening in accordance with the FDA animal rule.
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).
authors.affiliation: Division of Translational Radiation Sciences, Dept of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Jackson
authors.forename: Puting
authors.initials: P
authors.lastname: Xu
authors.forename: Caroline
authors.initials: C
authors.lastname: Hadley
authors.forename: Barry P
authors.initials: BP
authors.lastname: Katz
authors.forename: Ross
authors.initials: R
authors.lastname: McGurk
authors.forename: Julian D
authors.initials: JD
authors.lastname: Down
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
mesh_terms: D054508:Acute Radiation Syndrome / Q000209:etiology* / Q000503:physiopathology; D017087:Animal Rights; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D008403:Mass Screening / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000503:physiopathology; D017564:Radiation Pneumonitis / Q000209:etiology* / Q000503:physiopathology*; D011835:Radiation Protection / Q000379:methods; D013045:Species Specificity; D016019:Survival Analysis; D015996:Survival Rate; D014481:United States; D014486:United States Food and Drug Administration; D014916:Whole-Body Irradiation / Q000009:adverse effects*