Marginal zinc intake reduces the protective effect of lactation on mammary gland carcinogenesis in a DMBA-induced tumor model in mice

Bostanci,Zeynep; Mack,Ronald  P.; Enomoto,Laura   M.; Alam,Samina; Brown,Ashley; Neumann,Carola; Soybel,David  I.; Kelleher,Shannon  L.

doi:10.3892/or.2015.4508

Marginal zinc intake reduces the protective effect of lactation on mammary gland carcinogenesis in a DMBA-induced tumor model in mice

Authors:
- Zeynep Bostanci
- Ronald P. Mack
- Laura M. Enomoto
- Samina Alam
- Ashley Brown
- Carola Neumann
- David I. Soybel
- Shannon L. Kelleher
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Affiliations: Department of Surgery, The Pennsylvania State University Hershey College of Medicine, Hershey, PA 17033, USA, Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, P.R. China, Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15260, USA
Published online on: December 22, 2015 https://doi.org/10.3892/or.2015.4508
Pages: 1409-1416

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Abstract

Breastfeeding can reduce breast cancer risk; however, unknown factors modify this protective effect. Zinc (Zn) modulates an array of cellular functions including oxidative stress, cell proliferation, motility and apoptosis. Marginal Zn intake is common in women and is associated with breast cancer. We reported that marginal Zn intake in mice leads to mammary gland hypoplasia and hallmarks of pre-neoplastic lesions. In the present study, we tested the hypothesis that marginal Zn intake confounds the protective effect of lactation on breast cancer. Nulliparous mice fed control (ZA, 30 mg Zn/kg) or a marginal Zn diet (ZD, 15 mg Zn/kg), were bred and offspring were weaned naturally. Post-involution, mice were gavaged with corn oil or 7,12-dimethylbenz(a)anthracene (DMBA, 1 mg/wk for 4 weeks) and tumor development was monitored. A ZD diet led to insufficient involution, increased fibrosis and oxidative stress. Following DMBA treatment, mice fed ZD had higher oxidative stress in mammary tissue that correlated with reduced levels of peroxiredoxin-1 and p53 and tended to have shorter tumor latency and greater incidence of non-palpable tumors. In summary, marginal Zn intake creates a toxic mammary gland microenvironment and abrogates the protective effect of lactation on carcinogenesis.

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