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A reliable test for premalignant lesions in the development of colonic cancer in chronic ulcerative colitis has been needed. Thus, we designed this cytochemical study, using a model of experimental colitis and colonic tumors induced in Wistar male rats by the feeding of dextran sulfate sodium. The colitis had histologic similarities to ulcerative colitis in man. The percent frequency of polypoid lesions (dysplasia or dysplasia with carcinoma in situ) in the cecum and ascending colon was about 25% at three months and 90% at six months of dextran sulfate feeding. The cytochemical findings by high-iron diamine-Alcian blue staining and Ulex europeus agglutinin binding were chronologically paralleled by histological changes in the colonic mucosa, and the binding pattern of peanut agglutinin was not different between normal and dextran-treated animals. Moreover, some cytochemical changes that occurred during the inflammatory responses were not present in dysplastic or malignant lesions. Thus, the histochemical tests were not useful for detecting of premalignant lesions earlier than by conventional histology. Nevertheless, the dextran sulfate model of colitis in the rat appears suitable for study of cancer development in ulcerative colitis.

The vasoactive intestinal peptide concentration was examined in the colonic wall and portal venous plasma of rats with chemical colitis by radioimmunoassay, and the colonic localization was determined with immunocytochemistry. Colonic acetylcholine esterase activity was also measured, and the response of vasoactive intestinal peptide to acetylcholine administration was determined. Colitis was induced by administration of dextran sulfate for three months. The chemical colitis was histologically similar to active human ulcerative colitis. We observed a significant increase of immunostained neurons and nerve fibers and a significant rise in the colonic wall vasoactive intestinal peptide content in chemical colitis rats, while plasma concentrations of the peptide did not change significantly. Colonic acetylcholine esterase activity was significantly elevated in colitis rats compared with control rats. Systemic administration of acetylcholine significantly increased the colonic and plasma vasoactive intestinal peptide concentrations in colitis rats. These findings demonstrated a positive association between colitis activity and an increase of vasoactive intestinal peptide and suggested that increased vagal tone promoted the peptide's release.

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