FOLIC-ACID SUPPLEMENTATION AND CELL-KINETICS OF RECTAL MUCOSA IN PATIENTS WITH ULCERATIVE-COLITIS

It has been suggested that colon cancer risk in ulcerative colitis (UC ) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proli feration in patients affected by long-standing UC. In the rectal mucos a of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an interme diate biomarker in chemoprevention trials, Twenty-four patients (13 ma les; age, 26-70 years; UC duration, 7-34 years),vith UC in remission f or 1 month at least were assigned randomly to one of the following tre atments: (a) folinic acid (15 mg/day) or (b) placebo, Cell proliferati on was analyzed through immunohistochemistry on sections of rectal bio psies incubated for 1 hour in a culture medium containing bromodeoxyur idine, Fragments were taken at admission to the study and after 3 mont hs of treatment, As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reductio n of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P < 0.01), On the contrary, no significant proliferative changes were observed in the placebo group, These results suggest that folate supplementation contributes to regulating rectal cell prolifer ation in patients with long-standing UC. These findings may be signifi cant for chemoprevention of colon cancer in these patients.