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

• Published in: Oncology reports Vol. 35; no. 3; pp. 1409 - 1416
• Main Authors: BOSTANCI, ZEYNEP, MACK, RONALD P, ENOMOTO, LAURA M, ALAM, SAMINA, BROWN, ASHLEY, NEUMANN, CAROLA, SOYBEL, DAVID I, KELLEHER, SHANNON L
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.03.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - toxicity; Animals; Antioxidants; Apoptosis - drug effects; Breast cancer; Breast Neoplasms - chemically induced; Breast Neoplasms - diet therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breastfeeding & lactation; Carcinogenesis - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Transformation, Neoplastic - drug effects; collagen; Development and progression; Diet; Enzymes; Female; Health aspects; Humans; involution; Laboratory animals; Lactation; Lactation - genetics; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - pathology; Metabolism; Metastasis; Mice; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Peroxiredoxins - biosynthesis; Proteins; Rodents; Studies; Tumor Suppressor Protein p53 - biosynthesis; Tumors; Weaning; Womens health; zinc; Zinc - administration & dosage; Zinc in the body; United States > US
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2015.4508

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.