Folate Deficiency Enhances the Development of Colonie Neoplasia in Dimethylhydrazine-treated Rats1

In patients with ulcerative colitis, epidemiolÃ3gica!work has suggested an association between low folate status and an increased risk of colonie neoplasia. The aim of the present study was to determine if experimen tal folate deficiency increases the likelihood of developing neoplasia in rats treated with the carcinogen dimethylhydrazine. Weanling male Sprague-Dawley rats were fed with an amino acid-defined diet contain ing either 8 or Omg/kg folie acid. After 5 weeks of defined diet, weekly s.c. injections of dimethylhydrazine (20 mg/kg) were administered to both groups. Serum, whole blood, liver, and colonie folate concentrations at the time of sacrifice were significantly lower in folate-depleted ani mals ( /' < 0.001). There were significant differences in the incidence of colonie neoplasia between the two groups after 20 weeks of dimethyl hydrazine exposure: folate-deficient rats had a greater incidence of dysplasia (6 of 7 versus 2 of 7 animals; P < 0.05) and carcinoma (6 of 7 versus 1 of 7 animals; P < 0.01). Furthermore, a significantly greater proportion of folate-replete rats than folate-deficient rats were free of neoplastic lesions (5 of 7 versus 0 of 7 animals; /' < O.OS). These results suggest that, in this animal model, folate deficiency increases the risk of malignancy when there is an underlying predispo sition to colorectal cancer.