Epithelial cell folate depletion occurs in neoplastic but not adjacent normal colon mucosa

Background & Aims: Restricted folate supply is associated with the development of carcinoma, and folate supplements have a protective effect in colorectal carcinoma. This effect may be mediated through correction of local folate deficiency. The aim of this study was to define the folate content of neoplastic colonic epithelial cells and its relation to that of adjacent normal tissue and circulating levels. Methods: Epithelial cells were isolated from endoscopic biopsy specimens of normal, adenocarcinoma, adenoma, and adjacent normal colonic mucosa by ion chelation. Intracellular folate levels weve determined by microbiological assay. Results: Folate levels in carcinoma specimens were lower than in adjacent normal tissue (P < 0.02). Levels in adenoma epithelial cells were lower than in adjacent normal tissue, although this did not reach statistical significance (P < 0.06). Epithelial cells from normal tissue and mucosa adjacent to tumors and adenomata had similar folate contents. Blood folate and vitamin B-12 indices for all groups were normal. Conclusions: Malignant colon epithelial cells show a relative localized folate deficiency. However, there is no evidence for the occurrence of generalized mucosal folate deficiency. This finding suggests that folate supplements do not inhibit carcinogenesis through correction of localized folate depletion.