title: Folate exacerbates the effects of ethanol on peripubertal mouse mammary gland development.
abstract: Alcohol consumption is linked with increased breast cancer risk in women, even at low levels of ingestion. The proposed mechanisms whereby ethanol exerts its effects include decreased folate levels resulting in diminished DNA synthesis and repair, and/or 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, and that folate deficiency alone might mimic and/or exacerbate the effects of ethanol. To test this hypothesis, weight-matched 28-35 day old CD2F1 female mice were pair-fed liquid diets ±3.2% ethanol, ±0.1% folate for 4 weeks. Folate status was confirmed by assay of liver and kidney tissues. In folate deficient mice, no significant ethanol-induced changes to the mammary gland were observed. Folate replete mice fed ethanol had an increased number of ducts per section, due to an increased number of terminal short branches. Serum estrogen levels were increased by ethanol, but only in folate replete mice. 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.
authors.affiliation: Department of Biotechnical and Clinical Laboratory Sciences, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 14214, USA. pmwelch@buffalo.edu
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Masso-Welch
authors.forename: Menachem E
authors.initials: ME
authors.lastname: Tobias
authors.forename: Shyam C
authors.initials: SC
authors.lastname: Vasantha Kumar
authors.forename: MaryLou
authors.initials: M
authors.lastname: Bodziak
authors.forename: Terry
authors.initials: T
authors.lastname: Mashtare
authors.forename: Judith
authors.initials: J
authors.lastname: Tamburlin
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Koury
mesh_terms: D000818:Animals; D004958:Estradiol / Q000097:blood; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005492:Folic Acid / Q000378:metabolism / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000503:physiopathology*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development*; D051379:Mice
chemical_list: D000431:Ethanol; D004958:Estradiol; D005492:Folic Acid