Epidermal growth factor enhances intestinal mitotic activity and DNA content after acute abdominal radiation

Background. Mediators of radiation-induced enteritis and colitis remain undefined. Epidermal growth factor (EGF) is an endogenous peptide that is trophic to the gastrointestinal tract. We tested the hypothesis that EGF enhances DNA synthesis and mitotic activity and prevents acute radiation enteritis after total abdominal radiation. Methods. Four equal groups (n = 6) of Sprague-Dawley rats were studied: I (control), II (radiation), III (EGF), and IV (radiation + EGF). Animals in groups III and IV received EGF (10 μg/kg) every 8 hours for 48 hours before radiation exposure and for 72 hours after radiation, and the remaining animals were given an equal volume of vehicle. Animals in groups II and IV were administered a single dose of abdominal radiation (1000 cGy) 48 hours after the start of either vehicle or EGF. Distal ileum and colon were harvested 72 hours after radiation, examined histologically, and assayed for total DNA content. Results. Group II or radiated animals had diarrhea, significant weight loss (p < 0.05), and decreased food consumption consistent with acute clinical radiation enteritis. Mitotic activity and total DNA content were significantly reduced (p < 0.05) when compared with group I (nonradiated controls). Group IV animals treated with EGF and exposed to radiation did not suffer the acute clinical manifestations of radiation enteritis. In addition, total DNA content and mitotic activity of the terminal ileum increased significantly (p < 0.05), and a significant increase in mitotic activity occurred in the distal colon when compared with radiated controls. Conclusions. The results of this study suggest that (1) a decrease in mitotic activity and total DNA content occurs early and persists for at least 72 hours after acute radiation, (2) EGF treatment significantly increases small and large bowel mitogenicity in acutely radiated animals, and (3) EGF significantly decreases the acute clinical manifestations of radiation enteritis.