Effects of chronic alcohol consumption and folate supplementation on the mouse mammary gland
Tobias, Menachem E.
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Chronic alcohol consumption is a strong risk factor for breast cancer development in women. One potential mechanism linking alcohol and an increased risk of breast cancer development includes the ability for alcohol to reduce bio-available folate. It is not known how alcohol alters the structure of the mouse mammary gland to render it susceptible to carcinogenesis or whether folate supplementation may counteract the adverse effects of alcohol. The purpose of this research project was to test the hypothesis that dietary folate can beneficially alter the morphologic and histologic status of the mammary glands of mice on alcohol diets. This study was performed using thirty-two pre-pubertal female mice during an intermediate length feeding regimen. Diets included alcohol, folate, or both. Folate content of the liver and kidney was determined by bioassay using folate-dependent Lactobacillus casei . Assessment of morphological changes in the mammary gland structure was performed using mammary gland whole mounts analyzed for changes in the specific types of branches and terminal structures of the ductal system. Evaluation of histological changes in the mammary gland structure was performed using paraffin sections analyzed for microscopic formational changes in the ductal epithelium (cell composition) and stroma (surrounding tissue matrix). Present results indicate that mice on folate deficient diets had significantly less bio-available folate than those on folate supplementation and that folate levels were even lower when alcohol was consumed. Whole mount analysis revealed that alcohol consumption, in the presence of folate, allowed for an increase in mammary gland ductal branching. The consumption of alcohol also increases the percentage of highly proliferative terminal ductal structures. Paraffin section analysis as well revealed that alcohol consumption, in the presence of folate, allowed for an increase in mammary gland ductal density. The consumption of alcohol, in the presence of folate, additionally yielded an increase in the percentage of ductal epithelium area, and decrease in the percentage of ductal luminal area. The consumption of alcohol, in the presence of folate, furthermore increased the incidence of ductal epithelial hyperplasia, and, both in the presence and absence of folate, inhibited ductal secretory activity. These results suggest that the consumption of alcohol not only depletes the amount of bio-available folate, but also alters the structure of the mouse mammary gland to render it more susceptible to carcinogenesis.