Carcinogenesis Advance Access originally published online on May 11, 2005
Carcinogenesis 2005 26(9):1603-1612; doi:10.1093/carcin/bgi117
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Carcinogenesis vol.26 no.9 © Oxford University Press 2005; all rights reserved.
Effects of dietary folate on the development and progression of mammary tumors in rats
1 Department of Nutritional Sciences, 2 Department of Medicine, 3 Division of Comparative Medicine and 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, 5 Inner City Health Research Unit and 6 Department of Medicine, St Michael's Hospital, Toronto, Ontario, Canada
* To whom correspondence and reprint requests should be addressed at: Room 7258, Medical Sciences Building, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada, M5S 1A8; Tel: +1 416 978 1183; Fax: +1 416 978 8765; Email: youngin.kim{at}utoronto.ca
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.
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