IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
capítulos de libros
Título:
The Organophosphorus Chlorpyrifos as a Breast Cancer Risk Factor
Autor/es:
C VENTURA; M NUÑEZ; A RANDI; A VENTURINO; C COCCA
Libro:
Chlorpyrifos: Toxicological Properties, Uses and Effects on Human Health and the Environment
Editorial:
Nova Science Publishers, Inc.
Referencias:
Año: 2015; p. 15 - 27
Resumen:
Organophosphate pesticides comprise a group of substances used in agriculture for insect and plague control, infestations in buildings, man or domestic animals. The use of insecticides represents an environmental risk due to the high mass of product applied annually. Chlorpyrifos (CPF) is a broad-spectrum-organophosphate pesticide. The primary target of CPF toxicity is the central and peripheral nervous system, due to its ability to inhibit the acetylcholinesterase activity. However, other actions of CPF as the effects on synthesis of macromolecule like DNA, RNA and proteins, interactions with neurotransmitter receptors and other neurochemical affections were described. Breast cancer is the most frequent malignant disease in women. Exposure to estrogens throughout womanas life is a risk factor for this malignancy. Estrogen receptor alpha (ERalpha) is the major regulator of breast cancer tumor behavior. In the mammary gland, 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 ERalpha responses. Moreover, CPF possesses antiandrogenic activity and significantly decreases testosterone biosynthesis. We demonstrated the ability of CPF environmental concentration to induce cell proliferation through ERalpha 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 hydrogen peroxide production induced by CPF. In vivo, we have recently observed that virgin rats exposed to CPF present a proliferative mammary tissue similar to the pregnant state, lower estradiol circulating levels and a prolonged estrous cycle. These results point to CPF as an ED stimulating the mammary gland proliferation and altering the estrogenic balance at systemic levels. Taken all this into account, the use of CPF should be strictly controlled considering that this pesticide could affect human or animal health and environment.