IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Clorpirifos is an endocrine disrupter mammary gland and interferes with cell growth regulation
Autor/es:
NÚÑEZ, MARIEL; A RANDI; C VENTURA; C COCCA
Lugar:
Montevideo
Reunión:
Simposio; X Congress of ALAMCTA; 2016
Resumen:
Chlorpyrifos (CPF) is a broad-spectrum-organophosphate pesticide used as an insecticide in our region. The main mechanism of CPF toxicity is the acetylcholinesterase activity inhibition. However, CPF may also affect DNA, RNA and proteins regulation. Breast cancer is the most frequent malignant disease in women. Exposure to estrogens throughout woman?s life is a risk factor for this malignancy. In the mammary gland, 17β-estradiol (E2) promotes cell proliferation in both normal and transformed epithelial cells by modifying the expression of hormone responsive involved genes. Endocrine disrupter (ED) is defined as a compound of industrial or natural origin that interferes with hormone biosynthesis, action and metabolism, resulting in a deviation from normal homeostatic control or reproduction. CPF was recognized as an ED since it has been demonstrated to possess the ability to interfere with the ERα responses. We found that environmental concentrations of CPF induce cell proliferation through ERα in hormone-dependent MCF-7 breast cancer cells. In contrast, higher doses of CPF promoted cell cycle arrest in S?phase modifying checkpoints proteins, through a mechanism that may involve changes in redox balance in MCF-7 cells. In hormone-non-dependent MDA-MB-231 cells, we demonstrated that CPF is not able to promote cell proliferation but induces G2/M cell cycle arrest. In breast cancer cells, CPF induces redox imbalance, which lead to the cell cycle arrest. In turn, redox imbalance was trigged by an increment of p-ERK1/2 levels which is a result of an increment of CPF-induced hydrogen peroxide production. In female Sprague-Dawley rats, the pesticide reduced the expression of co-repressors of estrogen receptor activity REA and SMRT and it decreased serum E2, progesterone and luteinizing hormone (LH) levels. Finally, we found a persistent decrease in LH levels among ovariectomized rats exposed to CPF. Therefore, CPF alters the endocrine balance acting as an ED in vitro and in vivo.