Structural and functional alterations of the gastrointestinal tract following radiation-induced injury in the rhesus monkey

A severe and debilitating diarrhea is a dose-limiting toxic result for patients receiving abdominal radiation or chemotherapy. To correlate changes in intestinal structure and function, nonhuman primates were exposed to 9.5 Gy total abdominal x-irradiation. Diarrhea and weight loss were correlated with intestinal crypt and villus histology, in vivo assessed intestinal permeability, and ex vivo functional studies performed in Ussing chamber assays before and at 7, 14, and 35 days after irradiation. Peak gut structural damage occurred early and paralleled functional changes of the intestinal mucosa, including increased epithelial permeability (both in vivo and ex vivo), activation of secretory pathways, decreased nutrient absorption, diarrhea, and weight loss. Recovery of gut integrity and epithelial resistance began thereafter, in spite of incomplete histological recovery. Our integrated approach allowed a comprehensive study of the relationship between postirradiation tissue injury and changes in function over time in the gastrointestinal tract of the nonhuman primate.