Folic acid mediated prevention of LOH of tumor suppessor genes in colorectal adenomas
Nagothu, K.K.mar; Moragoda, L.; Rishi, A.K.mar; Jaszewski, R.; Majumdar, A.P.N., 2002: Folic acid mediated prevention of LOH of tumor suppessor genes in colorectal adenomas. FASEB Journal 16(5): A789, March 22
Loss of heterozygosity (LOH) of tumor suppressor genes are implicated in the development of many malignancies. Although supplemental folic acid appears to decrease the risk of colon cancer, the underlying mechanism(s) is poorly understood. To determine the role of folic acid in modulating the mutational status of tumor suppressor genes in the colon, we investigated the incidence of LOH of DCC, APC and p53 genes in normal appearing colonic mucosa from 20 patients with adenomatous polyps, who received either folic acid (5mg/day) or placebo for a year. LOH was analyzed by PCR amplification using primers for DCC, APC and p53. The protein levels were determined by Western-blot. Folic acid supplementation produced 100% stability of DCC gene (4/4), compared to 50% in the placebo-treated group. Mucosal protein levels of DCC were reduced in placebo, but not in folic acid treated patients. However, folic acid caused no change in allelic status of either APC or p53 gene. Observation that folic acid prevents LOH of DCC gene and stabilizes its protein in mucosa of patients with adenomas suggests that the vitamin may exert its chemopreventive role by stabilizing certain tumor suppressor gene(s).Other references