Folate Deficiency Enhances the Development of Colonic Neoplasia in Dimethylhydrazine-treated Rats

Marilia L. Cravo; Joel B. Mason; Yogeshwar Dayal; Martha Hutchinson; Donald Smith; Jacob Selhub; Irwin H. Rosenberg

DOI: Published September 1992

Abstract

In patients with ulcerative colitis, epidemiological work has suggested an association between low folate status and an increased risk of colonic neoplasia. The aim of the present study was to determine if experimental 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 containing either 8 or 0 mg/kg folic 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 colonic folate concentrations at the time of sacrifice were significantly lower in folate-depleted animals (P < 0.001). There were significant differences in the incidence of colonic neoplasia between the two groups after 20 weeks of dimethylhydrazine 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; P < 0.05).

These results suggest that, in this animal model, folate deficiency increases the risk of malignancy when there is an underlying predisposition to colorectal cancer.

Footnotes

↵¹ Supported in part with Federal funds from the U.S. Department of Agriculture, Agricultural Research Service Contract 53-3K06-0-1. The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
↵² M. L. C. was supported in part by a grant from INVOTAN INV/FRH 12/89, Lisbon, Portugal. Present address: Serviço de Gastroenterologia, Instituto Portugues de Oncologia Francisco Gentil, Lisboa, Portugal.
↵³ J. B. M. was supported in part by a Future Leader in Nutrition Award from the International Life Science Institute. To whom requests for reprints should be addressed, at Vitamin Bioavailability Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111.