The organophosphorus chlorpyrifos as a breast cancer risk factor

CLARA VENTURA; MARIEL NÚÑEZ; ANDREA RANDI; ANDRES VENTURINO; CLAUDIA COCCA

CHLORPYRIFOS: TOXICOLOGICAL PROPERTIES, USES AND EFFECTS ON HUMAN HEALTH AND THE ENVIRONMENT

NOVA SCIENCE PUBLISHERS, INC

Lugar: Nueva York; Año: 2015; p. 1 - 15

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 riskdue to the high mass of product annually applied. Chlorpyrifos (CPF) is a broad spectrumorganophosphate pesticide. The primary target of CPF toxicity isthe central and peripheral nervous system, due to its ability toinhibit the acetylcholinesterase activity. However,other actions of CPF as the effects on synthesis of macromolecule like DNA, RNA and proteins, interactionswith neurotransmitter receptors and other neurochemical affectionswere described.Breast cancer is the most frequent malignant disease in women.Exposure to estrogens throughout woman?s life is a risk factorfor this malignancy. Estrogen receptoralpha (ERα) is the major regulator of breast cancer tumor behavior. In the mammary gland, 17β-estradiol (E2) promotes cellproliferation in both normal and transformed epithelial cells bymodifying the expression of hormone responsive genes involved. Endocrine disrupter (ED) is defined as a compound of industrial or natural origin that interfere with hormonebiosynthesis, action and metabolism, resulting in a deviation fromnormal homeostatic control or reproduction. CPFwas recognized as an ED since it has been demonstratedto possess the ability to interfere with the ERαresponses. Moreover,CPF has antiandrogenicactivity and significantly decreases testosterone biosynthesis. We demonstrated the ability of environmental concentration of CPF to induce cell proliferation through ERα in hormone-dependent MCF-7 breast cancer cells. In contrast, higher doses of CPFpromoted cell cycle arrestin S?phase modifying checkpoints proteins, through a mechanismthat 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 ofhydrogen 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.