title: Paradoxical zinc toxicity and oxidative stress in the mammary gland during marginal dietary zinc deficiency.
abstract: Zinc (Zn) regulates numerous cellular functions. Zn deficiency is common in females; ∼80% of women and 40% of adolescent girls consume inadequate Zn. Zn deficiency enhances oxidative stress, inflammation and DNA damage. Oxidative stress and inflammation is associated with breast disease. We hypothesized that Zn deficiency increases oxidative stress in the mammary gland, altering the microenvironment and architecture. Zn accumulated in the mammary glands of Zn deficient mice and this was associated with macrophage infiltration, enhanced oxidative stress and over-expression of estrogen receptor α. Ductal and stromal hypercellularity was associated with aberrant collagen deposition and disorganized e-cadherin. Importantly, these microenvironmental alterations were associated with substantial impairments in ductal expansion and mammary gland development. This is the first study to show that marginal Zn deficiency creates a toxic microenvironment in the mammary gland impairing breast development. These changes are consistent with hallmarks of potential increased risk for breast disease and cancer.
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, United States; Department of Surgery, Penn State Hershey College of Medicine, United States.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Bostanci
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, United States; Department of Kinesiology, The Pennsylvania State University, United States.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mack
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, United States; Interdisciplinary Graduate Program in Physiology, The Pennsylvania State University, United States.
authors.forename: Sooyeon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, United States; Department of Surgery, Penn State Hershey College of Medicine, United States; Department of Cell and Molecular Physiology, Penn State Hershey College of Medicine, United States.
authors.forename: David I
authors.initials: DI
authors.lastname: Soybel
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, United States; Interdisciplinary Graduate Program in Physiology, The Pennsylvania State University, United States; Department of Surgery, Penn State Hershey College of Medicine, United States; Department of Cell and Molecular Physiology, Penn State Hershey College of Medicine, United States. Electronic address: slk39@psu.edu.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Kelleher
mesh_terms: D000367:Age Factors; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D003094:Collagen / Q000378:metabolism; D003677:Deficiency Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008264:Macrophages / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D018570:Risk Assessment; D015032:Zinc / Q000378:metabolism* / Q000633:toxicity
chemical_list: D027682:Cation Transport Proteins; D047628:Estrogen Receptor alpha; D003094:Collagen; D015032:Zinc
keywords: Breast cancer; Collagen; Ductal hyperplasia; Estrogen receptor; Mammary gland; Oxidative stress; Zinc transporter
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