title: Marginal zinc intake reduces the protective effect of lactation on mammary gland carcinogenesis in a DMBA-induced tumor model in mice.
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.
authors.affiliation: Department of Surgery, The Pennsylvania State University Hershey College of Medicine, Hershey, PA 17033, USA.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Bostanci
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, P.R. China.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mack
authors.affiliation: Department of Surgery, The Pennsylvania State University Hershey College of Medicine, Hershey, PA 17033, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Enomoto
authors.affiliation: Department of Surgery, The Pennsylvania State University Hershey College of Medicine, Hershey, PA 17033, USA.
authors.forename: Samina
authors.initials: S
authors.lastname: Alam
authors.affiliation: Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Brown
authors.affiliation: Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Carola
authors.initials: C
authors.lastname: Neumann
authors.affiliation: Department of Surgery, The Pennsylvania State University Hershey College of Medicine, Hershey, PA 17033, USA.
authors.forename: David I
authors.initials: DI
authors.lastname: Soybel
authors.affiliation: Department of Surgery, The Pennsylvania State University Hershey College of Medicine, Hershey, PA 17033, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Kelleher
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005260:Female; D006801:Humans; D007774:Lactation / Q000235:genetics; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D054464:Peroxiredoxins / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene; D054464:Peroxiredoxins; D015032:Zinc