PROMOTION OF COLORECTAL NEOPLASIA IN EXPERIMENTAL MURINE ULCERATIVE-COLITIS

Background-The mechanisms underlying the frequent development of color ectal carcinomas in patients with ulcerative colitis are still unknown . Aims-To evaluate whether mucosal necrosis and regeneration act as en hancing or promoting factors in colorectal tumorigenesis, development of multiple colorectal tumours was studied in a murine model of ulcera tive colitis with azoxymethane pretreatment. Methods-Periods of chroni c ulcerative colitis in mice were induced by three repeated administra tions of 3% dextran sulphate sodium subsequent to a single azoxymethan e pretreatment, to give conditions similar to the clinically observed active and remission phases. Results-In the chronic colitis group with carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the colorectum. This occurred primarily on the left side of the lar ge intestine or transverse colon, the sites of the most severe colitic injury. The observed lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell proliferation was evidenced by high up take of bromodeoxyuridine, and increased activities of thymidylate syn thetase and thymidine kinase. No tumours were induced in the control g roups with azoxymethane pretreatment or chronic colitis alone. Conclus ions-Repeated mucosal erosion with necrosis and regeneration is critic al for the development of colorectal tumours in this experimental coli tis system.