Mesalazine changes apoptosis and proliferation in normal mucosa of patients with sporadic polyps of the large bowel

Background and Study Aims: Regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the occurence of colorectal adenoma and carcinom a, possibly by inducing apoptosis and/or decreasing proliferation in colore ctal epithelial cells. Mesalazine is widely used in the treatment of patien ts with inflammatory bowel disease, and well tolerated. We investigated its effect on apoptosis and proliferation of colorectal mucosa in 21 patients with sporadic polyps of the large bowel, Patients and Methods: In total, 17 patients with sporadic colorectal polyps (greater than or equal to 5 mm) underwent polypectomy and biopsy of uninvo lved mucosa before and after treatment with 1g/d mesalazine for 1, 3, 7 or 14 days. Four additional patients served as untreated controls, Apoptotic i ndex (AI) was measured by terminal deoxynucleotidyl transferase-mediated d- uridine triphosphate nick-end labeling (TUNEL) assay; proliferation index ( PI) was measured by immunohistochemical examination with anti-Ki67 antibody . Results: Al was significantly increased 1 and 3 days after initiation of tr eatment with mesalazine compared with controls (P = 0.0107 for the 1-day tr eatment group and P = 0,0142 for the 3-day treatment group), and seemed to remain largely unchanged after longer treatment duration. Proliferation app eared to be decreased by mesalazine in all treatment groups, while prolifer ation in controls did not change (P = 0,0107 for the 1-day treatment group and P = 0.0142 for the 3-day treatment group compared with controls. Conclusions: Mesalazine significantly induces apoptosis and decreases proli feration in colorectal mucosa in patients with sporadic polyps of the large bowel, This may be clinically relevant in that it may lower the rate of po lyp recurrence after polypectomy, thereby possibly contributing to the chem oprevention of sporadic colorectal carcinoma.