Studies of the effects of ionizing radiation on intestinal function have been hampered by inappropriate animal models.  Rodents, while commonly used and economical, exhibit a different radiosensitivity and range of biological responses compared to humans.  Furthermore, most studies examine the effects of total body (TB) radiation, since applying local, abdominopelvic (AP) irradiation is difficult in small species such as the mouse. Whereas mucosal dysfunction is observed in these species, radiation-induced inflammation is not.  Thus, we have compared TB and AP irradiation in the ferret, a larger species which exhibits the same radiosensitivity and biological response to irradiation as humans.  Methods.  Male Fitch ferrets (1-1.5 kg) were restrained and exposed to 5 Gy g-radiation (⁶⁰Co source; 1.25 Gy/min) applied either to the whole body or selectively to the abdominopelvic region. Shams were handled in the same manner but not exposed to the source.  At 2 and 7 days post-exposure, ferrets were killed and blood drawn for white blood cell counts.  Segments of jejunum, distal ileum and colon were taken for histology and for assay of myeloperoxidase (MPO) activity and iNOS mRNA expression as indicators of an inflammatory response. Results.  All irradiated ferrets exhibited prodromal symptoms including retching, vomiting and diarrhea in the first 2 hr post-exposure. Histology revealed little abnormality at the light microscopic level indicating that epithelial depletion was not a factor post-irradiation.  WBC counts were reduced following AP and virtually abolished by TB irradiation compared to shams.  MPO activity was increased in ileum of 2 day AP-, but not TB-treated ferrets indicating an acute inflammatory response.  MPO was virtually undetectable from all regions at 7 days in TB ferrets. iNOS mRNA expression, which we have shown is elevated in irradiated rodents, was present in shams and not increased in irradiated groups. Conclusions. AP irradiation is less likely to decimate circulating WBC populations, but more likely to induce ileal inflammation, than TB irradiation. The data suggest that the ferret is a more appropriate animal model of radiation enteritis than rodents, and that radiation-ileitis may be a factor in radiation-induced intestinal dysfunction in radiotherapy patients.  

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