Effect of epidermal growth factor administration on intestinal cell proliferation, crypt fission and polyp formation...

Recombinant epidermal growth factor (EGF) may be useful to treat severe ulcerative gastrointestinal injury. There is concern, however, that systemic use of this potent mitogen might increase tumour development and/or progression in susceptible subjects. We therefore examined the effect of chronic administration of systemic EGF to multiple intestinal neoplasia (Min ) mice, who have a genetic defect in the adenomatous polyposis coli (APC) gene, leading to increased polyp development. Min mice (n =26) and wild-type littermates (n =26) received saline or EGF (223 microg of EGF/kg per day) for 4 weeks using subcutaneous osmotic mini-pumps. Cell proliferation and crypt fission were analysed using microdissection techniques and the number and size of polyps in the small and large intestines were determined. EGF increased wet weight and crypt cell proliferation rate by approx. 20% (all P <0.01 compared with the relevant control) in the small intestine and colon of both control and Min mice. In both groups, EGF reduced the colonic fission index by approx. 40% (P <0.01), but did not affect crypt fission in the small intestine. In Min mice, administration of EGF did not increase numbers of polyps or degree of dysplasia, but resulted in a 40% increase in the polyp size in the proximal intestine (P <0.02), but not in the remainder of the small intestine or colon. No polyps were found in control mice given EGF. EGF did not initiate polyp formation in control or Min mice. However, as polyp size is an important determinant for subsequent risk of malignant change in human colon cancer, further studies appear justified.