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Gestational, lactational and juvenile exposure to dietary zinc supplementation or deficiency and susceptibility to mammary carcinogenesis in female Sprague-Dawley rats

Abstract

The present study aims to evaluate whether exposure to dietary zinc suplementation or deficiency during the stages of pregnancy, lactation and juvenile interferes with the development and differentiation of normal mammary gland structures and susceptibility to development of mammary carcinogenesis induced by 7,12- dimethylbenz(a)anthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant females will be distributed in three groups: groups receiving diets containing normal levels (0.012 mg/g), deficient (0.005 mg/g) or with supplementation (0.18 mg / g) of zinc during gestational day 10 (DG 10) until postnatal day 21 (PND 21). After weaning, the females offspring will be distributed in three groups (60 animals/group) receive the same diets as their dams until 51 DPN. Females SD are euthanized for removal of the mammary glands or receive a single dose of DMBA (50mg/kg, ig) for initiation of mammary carcinogenesis and euthanized on PND 53 or PND 160. In DPN 51 and 53, the blood will be collected for determination of serum zinc and analysis of plasma estrogen and progesterone, respectively. In the PND 51 mammary glands will be collected for analysis of total mount, morphology and immunohistochemical analysis. The mammary glands collected at PND 53 will be processed to evaluate the expression of genes related to DNA damage and repair, apoptosis, cell cycle and signaling genes related to estrogen receptor and p53 by RT-PCR in real time. Tumors collected throughout the experiment or the end of the DNP 160 will be processed for histological evaluation. The latency, incidence and multiplicity of mammary tumors will be compared among experimental groups. The results of this study will clarify possible genetic pathways altered by diets with different levels of zinc that might alter the susceptibility to mammary cancer, and validate these possible changes in an experimental model of mammary carcinogenesis. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE LIMA E SILVA, TASSIA C.; DA SILVEIRA, LIVIA T. R.; FRAGOSO, MARIANA F.; DA SILVA, FLAVIA R. M.; MARTINEZ, MEIRE F.; ZAPATERINI, JOYCE R.; DINIZ, ODAIR H. G.; SCARANO, WELLERSON R.; BARBISAN, LUIS F. Maternal Resveratrol Treatment Reduces the Risk of Mammary Carcinogenesis in Female Offspring Prenatally Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin. HORMONES & CANCER, v. 8, n. 5-6, p. 286-297, DEC 2017. Web of Science Citations: 5.
DA SILVAA, FLAVIA R. M.; GRASSI, TONY F.; ZAPATERINI, JOYCE R.; BIDINOTTO, LUCAS T.; BARBISAN, LUIS F. Early-in-life dietary zinc deficiency and supplementation and mammary tumor development in adulthood female rats. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 44, p. 71-79, JUN 2017. Web of Science Citations: 1.
ROMUALDO, GUILHERME RIBEIRO; GOTO, RENATA LEME; HENRIQUE FERNANDES, ANA ANGELICA; COGLIATI, BRUNO; BARBISAN, LUIS FERNANDO. Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis. Food and Chemical Toxicology, v. 96, p. 280-289, OCT 2016. Web of Science Citations: 8.

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