Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 6; no. 6; pp. 469 - 471
• Main Authors: Biasco, G, Zannoni, U, Paganelli, G M, Santucci, R, Gionchetti, P, Rivolta, G, Miniero, R, Pironi, L, Calabrese, C, Di Febo, G, Miglioli, M
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-06-1997
• Subjects: Adult; Aged; Biopsy; Cell Division; Colitis, Ulcerative - complications; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - pathology; Colorectal Neoplasms - etiology; Double-Blind Method; Female; Humans; Immunohistochemistry; Leucovorin - blood; Leucovorin - therapeutic use; Male; Middle Aged; Mitotic Index; Mucous Membrane - pathology; Prospective Studies; Rectum - pathology
• ISSN: 1055-9965; 1538-7755

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 proliferation in patients affected by long-standing
UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently.
This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70
years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments:
(a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal
biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study
and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic
acid, a significant reduction 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
proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in
these patients.