title: Effects of dietary folate on the development and progression of mammary tumors in rats.
abstract: Epidemiologic studies have suggested that dietary intake and blood levels of folate may be inversely related to the risk of breast cancer. However, epidemiologic evidence has not been consistent nor has it provided unequivocal support for this purported inverse relationship. Recent evidence has also raised a concern that folate supplementation may promote carcinogenesis if provided after neoplastic foci are established in the target organ. This study investigated the effect of dietary folate deficiency and supplementation on the development and progression of mammary tumors in the N-methyl-N-nitrosourea (MNU) rat model. Weanling, female Sprague-Dawley rats were fed diets containing 0, 2 (control) or 8 mg folic acid/kg diet during the initiation or the promotion phase of MNU-induced mammary tumorigenesis. At necropsy, all macroscopic mammary tumors were identified and histologically confirmed. Dietary folate deficiency and supplementation provided during the initiation phase did not significantly modulate the development of mammary tumors. In contrast, dietary folate deficiency provided during the promotion phase significantly inhibited the rate of appearance, incidence, mean volume and weight of adenocarcinomas compared with the control and supplemental diets. Folate supplementation provided during the promotion phase did not significantly modulate mammary tumorigenesis compared with the control group. These data indicate that moderate folate deficiency inhibits, whereas dietary folate supplementation at four times the basal dietary requirement does not promote, the progression of MNU-induced mammary neoplastic foci in this rat model. However, the limitations associated with the route and dose of MNU administration preclude a definitive conclusion concerning the effect of folate status on the initiation of MNU-induced mammary tumorigenesis.
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kotsopoulos
authors.forename: Alan
authors.initials: A
authors.lastname: Medline
authors.forename: Richard
authors.initials: R
authors.lastname: Renlund
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Sohn
authors.forename: Rochelle
authors.initials: R
authors.lastname: Martin
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Hwang
authors.forename: Suying
authors.initials: S
authors.lastname: Lu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Archer
authors.forename: Young-In
authors.initials: YI
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D016588:Anticarcinogenic Agents; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005494:Folic Acid Deficiency; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016588:Anticarcinogenic Agents; D008770:Methylnitrosourea; D005492:Folic Acid