Abstract 4576: Early-in-life dietary zinc supplementation or deficiency and susceptibility to mammary carcinogenesis in female Sprague-Dawley rat
Authors: Silva Flávia Regina Moraes , Bidinotto Lucas Tadeu , Carvalho Robson Francisco , Barbisan Luis Fernando 
Published: August 2015

Zinc deficiency during pregnancy and early postnatal life can adversely affect the health and predispose to an increased risk of developing chronic diseases at adulthood. The present study was designed to evaluate whether exposure to the dietary zinc supplementation or deficiency during the pregnancy, lactation and juvenile stages interferes with the development of mammary gland and susceptibility to the mammary carcinogenesis induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant females were allocated into three groups (n = 15 each): dams received diets containing normal levels (35mg/Kg), deficient (3mg/Kg) or with supplementation (180mg/Kg) of zinc during gestational day 10 (GD 10) until the weaning of litters. After weaning, the females offspring were allocated into three groups and received the same diets as their dams until postnatal day PND 51 or 53. On PND 51, females SD (n = 10, 1 pulp/litter) were euthanized for removal of the abdominal mammary tissue for whole mount analysis or received a single dose of DMBA (50mg/kg, ig) for initiation of mammary carcinogenesis and euthanized on PND 53 (n = 10, 1 pulp/litter) or PND 180 (n = 16, 1 pulp/litter). On PND 53, mammary glands were collected for cell proliferation, apoptosis and estrogen receptor alpha (ER-α) immunohistochemistry analyzes, as well as evaluation the expression of genes related to DNA damage and repair, apoptosis, cell cycle and signaling related to estrogen receptor and p53 by TaqMan Low-density Array (TLDA).Tumors collected at PND 180 were processed for histological evaluation. Male and female offspring from dams receiving dietary zinc deficiency presented a significant reduction in body weight on PND 0, 10, 21 e 51. The mean number of the terminal buds (TEBs), ducts terminal (TEDs) and alveolar buds (ABs) in mammary gland did not differ among the groups. Dietary zinc supplementation significantly increased the indexes of cell proliferation in the mammary glands in relation to the control group while the indexes of apoptosis and ER-α did not differ among the groups. Also, dietary zinc supplementation significantly led downstream of Api5 and Ercc1 target genes related to apoptosis inhibitor and DNA repair, respectively. Also, dietary zinc supplementation or deficiency did not significantly change the histological pattern, volume, latency, incidence or multiplicity of mammary tumors in relation to the control group. However, dietary zinc supplementation increased the tumors number in 72%. The present findings suggest that the treatment with zinc suplementation during the stages of pregnancy, lactation and juvenile could have increased the susceptibility to development of mammary tumors induced by DMBA.

Citation Format: Flávia Regina Moraes Silva, Lucas Tadeu Bidinotto, Robson Francisco Carvalho, Luis Fernando Barbisan. Early-in-life dietary zinc supplementation or deficiency and susceptibility to mammary carcinogenesis in female Sprague-Dawley rat. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4576. doi:10.1158/1538-7445.AM2015-4576