Chlorpyrifos organophosphorous pesticide differentially alters redox metabolism in estrogen-dependent and estrogen-independent breast cancer cells

C. VENTURA, M. NÚÑEZ, D. MARTINEL LAMAS, N. MOHAMAD, C. PONTILLO, A. RANDI, E. RIVERA, A. VENTURINO, C. COCCA

Congreso; International Congress of Environmental Health (ICEH 2012); 2012

Chlorpyrifos (CPF) is a broad spectrum organophosphorous pesticide (OPs) that is widely used throughout the world in agriculture and non-agriculture applications. Oxidative stress has been described in acute, chronic, and developmental exposure to OPs, in both animals and humans, as well as in some in vitro studies. Although reactive oxygen species (ROS) modulate various biological processes, they can cause severe damage to DNA, protein and lipids. It has been reported that moderate increase of ROS may stimulate cell proliferation and estrogens may induce oxidative stress in MCF-7 cells. Previously, we have studied the effect of CPF on cell proliferation in estrogen-dependent (MCF-7) and in estrogen-independent (MDA-MB-231) breast cancer cell lines. We observed that CPF 50 μM inhibits clonogenicity, increases the doubling time and induces apoptosis in both lines. The cell cycle analysis showed that MCF-7 and MDA-MB-231 cells are arrested at S and G2/M phases, respectively, when they were treated with CPF 50 μM. On the other hand, CPF at 5.10-2 μM stimulated MCF-7 cell proliferation and the phosphorylation of a tyrosine residue in position 537 in the estrogen receptor alpha, which resulted implicated in the pesticide action. In contrast, CPF did not affect MDA-MB-231 cells proliferation at any dose assayed. To understand the mechanism implicated in cell proliferation modulation by CPF exposure, we analyzed the effect of the pesticide on redox metabolism. Concentrations ranging from 5.10-2 to 50 μM were tested. We studied ROS content by flow citometry by staining cells with DCF-2DA. The activity enzymes implicated in redox balance such as catalase, superoxide dismutase (SOD) and glutation transferase (GST) were measured by spectrometry. Our results demonstrated that CPF 50 μM produces an increment of the ROS content in both cell lines (32% over control in MCF-7, 108% over control in MDA-MB-231, p