Opposing effects of in utero and prepubertal dietary flaxseed exposure on mammary tumorigenesis Leena A. Hilakivi-Clarke, Galem Khan, Anna Cabanes. Georgetown University, Washington, DC. Elevated estrogen levels in utero may increase, while prepubertal estrogenic exposures reduce the susceptibility to breast cancer. These opposing effects are suggested to be mediated by changes in the mammary gland morphology and expression of estrogen-regulated genes. Our goal is to identify dietary factors that modify estrogenicty in utero and during prepuberty, and thus reduce later risk of developing breast cancer. In this study, pregnant or prepubertal (between postnatal days 5 and 25) rats were fed isocaloric diets containing either 0%, 5% or 10% flaxseed. Flaxseed contains phytoestrogens (lignans), but also high levels of n-3 fatty acids. Earlier studies indicate that in utero exposure to some phytoestrogens increases and prepubertal exposure reduces carcinogen-induced mammary tumorigenesis. n-3 fatty acids have opposite effects: in utero exposure reduces and prepubertal exposure increases later breast cancer risk. We found that in utero exposure to 10% flaxseed diet increased mammary epithelial density (one-way ANOVA, p<0.01), lobular estrogen receptor (ER)-a protein levels (assessed using immunohistochemistry) (p<0.001), and the number of apoptotic cells (assessed using Tunel assay) (p<0.001). In addition, this exposure shortened DMBA-induced mammary tumor latency (p<0.02) and increased tumor multiplicity (p<0.03). Prepubertal exposure to 10% flaxseed diet also increased mammary epithelial density (p<0.03) and mammary ER-a levels (p<0.04), but reduced the number of targets for malignant transformation (terminal end buds) (p<0.03) and apoptosis (p<0.004). Similarly to in utero exposure, prepubertal 10% flaxseed exposure shortened mammary tumor latency (p<0.03) and increased tumor multiplicity (p<0.01). Feeding pregnant or prepubertal rats 5% flaxseed diet had no effect on any of these end-points. Our results suggest that feeding 10% flaxseed diet in utero through a pregnant dam or during prepuberty increases later risk of developing mammary tumors. This increase may be linked to increased mammary epithelial density and expression of ER-a in the developing mammary gland. Acknowledgements: This work was supported by the Breast Cancer Research Foundation AACR Abstract Number: R4787, 2003 AACR Abstract #973, 2003 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.