POSTNATAL EXPOSURE TO A GLYPHOSATE-BASED HERBICIDE INDUCES PRENEOPLASTICLESIONS AND BENIGN TUMORSINTHE MAMMARY GLAND OF WISTAR RATS.

ZANARDI MV; GUERRERO SCHIMPF M; GASTIAZORO MP; MUÑOZ DE TORO M; KASS L; VARAYOUD J; DURANDO M

Congreso; TOXILATIN 2018; 2018

The development of the mammary gland (MG) is a hormone-regulated event. Several factors like agrochemicals can dysregulate its growth, and make the MG more susceptible to cellular transformation.Glyphosate is a systemic broad spectrum herbicide extensively used to control weeds on both cropland and non-cropland areas. It has been demonstrated that commercial formulations (containing co-adjuvants) are more dangerous than the active principle itself. Furthermore, there are controversial results related to the classification of the herbicide glyphosate as a ?probably carcinogenic to humans?. Nowadays, the level of exposure to glyphosate has grown exponentially, mainly due to the use of transgenic seeds resistant to these products.Objective:The aim of this studywas to determine whether exposure of female rats to low-dose of a glyphosate-basedherbicide (GBH) during early postnatal development impacts negatively on the MG structureand promotesbenign tumors. Methodology:All animal handling and experimental techniques were approved by the Ethical Committee of the FBCB (UNL). Virgin female Wistar rats were injected subcutaneously with saline solution (Control, C; n=8) or with GBH using the reference dose (2 mg/kg/day; n=10) on postnatal days 1, 3, 5, and 7. Animals were sacrificed at 20 months of age, MG were obtained and processed for histology and immunohistochemistry. We evaluated: a) morphological changes, b) proportion of each epithelial structure (ie: ducts, alveoli) or adipose tissue, c) percentage of hyperplastic ducts (with four or more layers of epithelial cells), considered preneoplastic lesions, d) cellular proliferation and e)epithelial expression of estrogen receptor alpha (ERa) and progesterone receptor (PR). Results:In GBH treated rats, one out of ten animals developed a benign tumor histopathologically diagnosed as a fibroadenoma. The percentage of ducts, alveoli and adipose tissue was not affected by GBH exposure. However the percentage of hyperplastic ducts was higher in GBH-rats (C: 6.20.9 vs GBH: 11.31.30; p