Paradoxical zinc toxicity and oxidative stress in the mammary gland during marginal dietary zinc deficiency

Zeynep Bostanci, Ronald P. Mack, Sooyeon Lee, David I. Soybel, Shannon L. Kelleher

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalReproductive Toxicology
Volume54
DOIs
StatePublished - Jul 1 2015

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Oxidative stress
Human Mammary Glands
Toxicity
Zinc
Oxidative Stress
Breast Diseases
Inflammation
Macrophages
Poisons
Cadherins
Infiltration
Estrogen Receptors
DNA Damage
Breast
Collagen
Breast Neoplasms
DNA

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Bostanci, Zeynep ; Mack, Ronald P. ; Lee, Sooyeon ; Soybel, David I. ; Kelleher, Shannon L. / Paradoxical zinc toxicity and oxidative stress in the mammary gland during marginal dietary zinc deficiency. In: Reproductive Toxicology. 2015 ; Vol. 54. pp. 84-92.
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Paradoxical zinc toxicity and oxidative stress in the mammary gland during marginal dietary zinc deficiency. / Bostanci, Zeynep; Mack, Ronald P.; Lee, Sooyeon; Soybel, David I.; Kelleher, Shannon L.

In: Reproductive Toxicology, Vol. 54, 01.07.2015, p. 84-92.

Research output: Contribution to journalArticle

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