Acute gastrointestinal syndrome in high-dose irradiated mice

Catherine Booth, Gregory Tudor, Julie Tudor, Barry P. Katz, Thomas J. MacVittie

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing, and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources, and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data, the authors have generated dose response data in adult male mice maintained under identical conditions and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow, and lung) in the surviving mice. Lethal dose (LD30, LD50, and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. These data can be used to aid the design of good laboratory practice (GLP)-compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure.

Original languageEnglish (US)
Pages (from-to)383-399
Number of pages17
JournalHealth physics
Volume103
Issue number4
DOIs
StatePublished - Oct 1 2012

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Keywords

  • Acute radiation exposure
  • Biological factors
  • Gastrointestinal
  • Mice modeling
  • Radiation damage

ASJC Scopus subject areas

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

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