EPIDERMAL GROWTH-FACTOR ENHANCES INTESTINAL MITOTIC-ACTIVITY AND DNA CONTENT AFTER ACUTE ABDOMINAL RADIATION

Background. Mediators of radiation-induced enteritis and colitis remai n undefined. Epidermal growth factor (EGF) is an endogenous peptide th at is trophic to the gastrointestinal tract. We tested the hypothesis that EGF enhances DNA synthesis and mitotic activity and prevents acut e radiation enteritis after total abdominal radiation. Methods. Four e qual 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 mu g/kg) every 8 hours for 48 hours befor e radiation exposure and for 72 hours after radiation, and the remaini ng animals were given an equal volume of vehicle. Animals in groups II and IV were administered a single dose of abdominal radiation (1000 c Gy) 48 hours after the start of either vehicle or EGF. Distal ileum an d colon were harvested 72 hours after radiation, examined histological ly, and assayed for total DNA content. Results. Group II or radiated a nimals 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 ani mals treated with EGF and exposed to radiation did not suffer the acut e clinical manifestations of radiation enteritis. In addition, total D NA content and mitotic activity of the terminal ileum increased signif icantly (p < 0.05), and a significant increase in mitotic activity occ urred in the distal colon when compared with radiated controls. Conclu sions. The results of this study suggest that (1) a decrease in mitoti c activity and total DNA content occurs early and persists for at leas t 72 hours after acute radiation, (2) EGF treatment significantly incr eases small and large bowel mitogenicity in acutely radiated animals, and (3) EGF significantly decreases the acute clinical manifestations of radiation enteritis.