Alcohol consumption has been clearly linked with increased breast cancer risk in women, with risks incurred even at low levels of consumption. The proposed mechanisms whereby ethanol exerts its effects include decreased folate levels and diminished DNA repair capacity, coupled with acetaldehyde-generated DNA damage. Based on these proposed mechanisms, we hypothesized that ethanol would have increased deleterious effects during periods of rapid mammary gland epithelial proliferation, such as peripuberty. We also hypothesized that folate deficiency alone might mimic the effects of ethanol, and that folate deficiency would exacerbate the effects of ethanol. CD2/F1 female mice (N=8 per group) were pair-fed control and ethanol-containing liquid diets +/− 0.2g/L folate supplementation from 5 weeks until 9 weeks of age. Mice were sacrificed after this 4 week feeding regimen, and mammary glands were harvested for preparation of whole mounts and paraffin sections. Folate levels of liver and kidney were assessed to verify folate status. Analysis of mammary gland whole mounts revealed that mammary gland structure was significantly altered in folate-replete mice fed ethanol, compared to control-fed mice (no ethanol/ folate-replete). These ethanol/folate replete mice showed an increased total number of ductal branches, due to an increased number of terminal short branches; no effect was seen on the number of terminal end buds or primitive alveolar buds. Systematic histological analysis of paraffin sections using NIH Image J software revealed that diets containing ethanol in the presence of folate significantly increased the total number of ducts, ductal epithelial area, and number of ducts with epithelial multilayering. These results demonstrate that folate deficiency alone does not mimic the effects of ethanol, and that folate deficiency in the presence of ethanol blocks proliferative effects of ethanol on the mammary ductal tree. Future studies are examining the effects of peripubertal ethanol and folate exposure on gene expression in the mouse mammary gland.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2872.