Time-dependent changes in the luminal surface and mass of the rat colon during prolonged systemic treatment with epidermal growth factor

Background: Systemic treatment with epidermal growth factor (EGF) for 4 weeks increases the colonic mucosal weight and surface area. The present study was initiated to describe the time-dependent colonic changes during prolonged treatment with EGF. Methods: Forty-eight female Wistar rats were allocated into live groups receiving subcutaneous EGF treatment (150 mu g/kg/day) for 0 (controls), 1, 2, 3, or 3 weeks. EGF was administered in the weeks before they were killed. By means of modern stereologic techniques (point counting and vertical sections). the weights of the colonic wall layers and the luminal surface area were measured on histologic sections. The colon was subdivided into proximal and distal parts. Results: The weight of the total colon increased relatively more than the total body weight. After 1 week of treatment with EGF the surface area and wet weight of the total colon increased by 47% and 10%, and after 4 weeks by 62% and 37%, respectively. After 3 weeks the weight increase was mainly due to increased mucosal weight (by 65%, P < 0.01) and less prominently the submucosa (by 45%, P < 0.01) and the muscularis propria (by 32%, P < 0.01). On the basis of the wet weight increase, the proximal colon was more responsive to EGF treatment than the distal colon. Conclusions: Systemic treatment with EGF for 1 week increased the luminal surface area relatively more than the mass of the colon. Treatment with EGF for more than 1 week caused only a minor further surface area increase. whereas the colonic mass continued to increase in a time-dependent manner.