POSTNATAL EXPOSURE TO A GLYPHOSATE-BASED HERBICIDE INDUCES PRENEOPLASTIC LESIONS AND BENIGN TUMORS IN THE MAMMARY GLAND OF WISTAR RATS.

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

Congreso; ToxiLatin 2018. 2° Congresso Latino-americano de Toxicologia Clínico-laboratorial.; 2018

The development of the mammary gland (MG) is ahormone-regulated event. Several factors like agrochemicals can dysregulate itsgrowth, and make the MG more susceptible to cellulartransformation. Glyphosate is a systemic broad spectrum herbicideextensively used to control weeds on both cropland and non-cropland areas. It hasbeen demonstrated that commercial formulations (containing co-adjuvants) aremore dangerous than the active principle itself. Furthermore, there arecontroversial results related to the classification of the herbicide glyphosateas a ?probably carcinogenic to humans?. Nowadays, the level of exposure toglyphosate has grown exponentially, mainly due to the use of transgenic seedsresistant to these products. The aim of this study was to determine whether exposureof female rats to low-dose of a glyphosate-based herbicide (GBH) during early postnataldevelopment impacts negatively on the MG structure and promotes benign tumors.All animal handling and experimental techniques wereapproved by the Ethical Committee of the FBCB (UNL). Virgin female Wistar ratswere injected subcutaneously with saline solution (Control, C; n=8) or with GBHusing the reference dose (2 mg/kg/day; n=10) on postnatal days 1, 3, 5, and 7. Animalswere sacrificed at 20 months of age, MG were obtained and processed forhistology and immunohistochemistry. We evaluated: a) morphological changes, b) proportionof each epithelial structure (ie: ducts, alveoli) or adipose tissue, c) percentageof hyperplastic ducts (with four or more layers of epithelial cells),considered preneoplastic lesions, d) cellular proliferation and e) epithelial expressionof estrogen receptor alpha (ERa) and progesterone receptor (PR). In GBH treated rats, one out of ten animals developeda benign tumor histopathologically diagnosed as a fibroadenoma. The percentageof ducts, alveoli and adipose tissue was not affected by GBH exposure. Howeverthe percentage of hyperplastic ducts was higher in GBH-rats (C: 6.2±0.9 vs GBH: 11.3±1.30; p