EFFECT OF MODERATE ETHANOL-CONSUMPTION ON MAMMARY-GLAND STRUCTURAL DEVELOPMENT AND DNA-SYNTHESIS IN THE FEMALE RAT

Epidemiological and experimental evidence provides support for a positive association between alcohol consumption and the development of breast cancer. To examine a mechanism for this association, young female Sprague-Dawley rats were pair-fed liquid diets containing ethanol at 0%, 15%, 20%, and 25% of calories for 32 days. The structural development and DNA-labeling index of the mammary gland were determined. Ethanol consumption at 20% and 25% of calories increased the density of carcinogen-sensitive terminal end bud (TEB) structures and decreased the density of carcinogen-insensitive alveolar bud structures of the developing mammary gland as compared to ad lib-fed and pair-fed controls. Consumption of ethanol at 20% and 25% of calories was also associated with a significant enhancement in the DNA-labeling index of mammary gland TEB structures, the target tissue for chemically-induced rat mammary tumorigenesis. In a separate study, serum progesterone but not estradiol, was decreased for rats fed ethanol at 25% of calories as compared to ad lib-fed and pair-fed controls. Thus moderate ethanol consumption at 20% and 25% of calories can delay the maturation and increase TEB DNA synthesis of the normal rat mammary gland. These changes may be explained by an ethanol-associated decrease in serum progesterone, a hormone important for the maturation of the mammary gland epithelium in the young female rat.