Influence of ethanol intake on mammary gland morphology and cell proliferation in normal and carcinogen-treated rats.

Alcohol consumption has been reported to increase breast cancer risk in a majority of epidemiological studies and to enhance, at specific dietary concentrations, both the initiation and promotion stages of chemically induced rat mammary tumorigenesis. However, there is limited information regarding possible mechanisms for this effect. The present studies were conducted to examine a possible mechanism for the promoting effect of ethanol on chemically induced mammary tumorigenesis. The influence of chronic ethanol intake by female rats on the progress of differentiation and on the rate of target structure cell proliferation of the mammary gland was evaluated. Results of these studies indicate that ethanol intake at 20% and 30% of calories by female rats between the ages of 55 and 94 days (a period associated with the promotion stage of experimental mammary tumorigenesis) results in a delay in the differentiation of the mammary gland. This delay in gland maturation observed for rats consuming ethanol was evidenced by an increase in the quantity of less mature terminal-end bud (TEB) structures and a decrease in the quantity of more mature alveolar bud structures. The DNA labeling index of the target structure TEB increased significantly for rats consuming ethanol. These changes in mammary gland maturation and in TEB DNA labeling index were observed for both normal and carcinogen-treated rats consuming ethanol. Also, serum progesterone, but not estradiol, was significantly decreased for animals consuming ethanol at 30% of calories compared with isocaloric controls. The correlation of these changes in the mammary gland with the reported enhancement by ethanol of the promotion stage of experimental rat mammary tumorigenesis is discussed.