This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Carrier, J. Articles by Kim, Y.-I. Search for Related Content PubMed PubMed Citation Articles by Carrier, J. Articles by Kim, Y.-I.

Effects of Dietary Folate on Ulcerative Colitis-Associated Colorectal Carcinogenesis in the Interleukin 2- and ß₂-Microglobulin-deficient Mice

¹ Departments of Medicine, ² Laboratory Medicine and Pathobiology, and ³ Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada, and ⁴ Inner City Health Research Unit and ⁵ Division of Gastroenterology, Department of Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada

Folate supplementation may reduce the risk of colorectal dysplasia and cancer in subjects with chronic ulcerative colitis (UC). The interleukin (IL) 2- and ß₂-microglobulin (ß₂m)-deficient (IL-2^null x ß₂m^null) mice spontaneously develop colon cancer in the setting of chronic UC. This study investigated the effects of dietary folate on the development of UC-associated colon cancer in the IL-2^null x ß₂m^null mice. Weaning IL-2^null x ß₂m^null mice were randomized to receive 0 (deficient; n = 40), 2 (basal requirement; control; n = 46), or 8 (supplemented; n = 36) mg folate/kg diet for 32 weeks. At necropsy, all macroscopic colonic tumors were identified and histologically classified as dysplasia or adenocarcinoma. The incidence of high-grade lesions (high-grade dysplasia/carcinoma in situ and invasive adenocarcinoma) in the folate-supplemented group was 46% lower than that in the control group (35.3% versus 65.1%, P = 0.009). The incidence of high-grade lesions in the folate-deficient group was also 49% lower than that in the control group (33.3% versus 65.1%, P = 0.007). The higher mortality rate in the folate-deficient group compared with the other two groups (25% versus 6.5% and 5.6%, P < 0.02) partially accounted for the low incidence of high-grade lesions in this group. These data indicate that dietary folate supplementation at 4x the basal dietary requirement significantly suppresses UC-associated colorectal carcinogenesis in the IL-2^null x ß₂m^null mice. These data also suggest that folate deficiency may inhibit colorectal carcinogenesis in chronic UC. However, the high mortality observed in the folate-deficient group precludes a definitive conclusion concerning the effect of folate deficiency on UC-associated colorectal carcinogenesis in this model.