Histological Changes in Mouse Colon after Single- and Split-Dose Irradiation

Abstract

These studies were undertaken to determine the relationship between acute mucosal damage and late obstructions in the colorectal region in the mouse after exposure to radiation. Radiation doses that either permanently depleted the mucosal epithelial cells or spared the mucosal lining by allowing epithelial regeneration were used. The distal 2.5 cm of colon and rectum of male C3Hf/Kam mice was irradiated with either a range of single doses (15-35 Gy) or two equal doses ranging from 9.75 to 14.75 Gy separated by 10 days. The time of onset and the incidence of obstructions and strictures in the bowel were recorded as a function of dose and time after irradiation. Acute damage in the mucosa and subsequent histological changes in the bowel were documented by sequential histological studies. Doses greater than 20 Gy caused acute crypt depletion followed by nonproductive attempts at regeneration and repopulation that culminated in persistent epithelial denudation. In these mice, obstructions appeared as early as 4 weeks and were characterized histologically by a mucosal ulceration extending deep into the muscularis. Single doses of less than 20 Gy and the split doses produced acute crypt cell depletion followed by successful regeneration, repopulation, and restoration of the colonic mucosa. In these mice, obstructions did not appear until at least 40 weeks after irradiation and were characterized by an intact mucosa with a thickened and fibrotic submucosa. Animals given a single dose of 20 Gy developed obstructions throughout the duration of the experiment. Those obstructions that occurred before 6 months were characterized by ulcerations, whereas those that appeared after this time exhibited only fibrosis in the submucosa with no mucosal ulceration. Based on these data, we suggest that two types of late obstructions occur in the bowel, one that depends on persistent epithelial denudation, i.e., a "consequential" response, and the other in the absence of epithelial denudation, i.e., a true late effect.