Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model

Background: As an important mechanism underlying the increased risk of colorectal carcinoma development in patients with long-standing ulcerative colitis, promotion as a result of the regenerative process has been proposed. In the present study, a dysplasia-carcinoma sequence in a novel repeated colitis model in mice is documented. Methods: Repeated colitis was induced by nine administration cycles of 3% dextran sulfate sodium (DSS; molecular weight, 54 000): each administration cycle comprised 3% DSS for 7 days followed by distilled water for the subsequent 14 days, to give conditions similar to the clinically observed active and remission phases in humans. Results: Multiple colorectal tumors (nine low- and four high-grade dysplasias and two carcinomas) developed in 25 mice. These neoplastic lesions consisted of tubular structures, presenting as various types of elevated, flat and depressed tumor, similar to those in ulcerative colitis patients. A time-course study with assessment of the severity of colitis and in vivo bromodeoxyuridine uptake during a single 3% DSS administration cycle revealed a high level of regenerative activity in the colitis-affected mucosal epithelia. Conclusion: Thus, with the present repeated colitis model, regeneration and neoplastic lesions were apparent, the biological features of which provide evidence of a colorectal dysplasia-invasive carcinoma sequence in ulcerative colitis. (C) 2002 Blackwell Publishing Asia Pty Ltd.