CHLORPYRIFOS PRODUCES DISSIMILAR EFFECTS ON PROLIFERATION IN BREAST CANCER CELLS 1

VENTURA C ; NÚÑEZ M; GAIDO V; UBERTONE CORRALES V; MARTINEL LAMAS D; RANDI A; VENTURINO A; RIVERA E; COCCA C

Puerto Madryn

Congreso; 46th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

A large body of literature suggests that environmental chemicals are involved in breast carcinogenesis. It has been postulated the use of the organophosphorus chlorpyrifos for replacing the current pesticide for fruit-bearing trees treatment in Alto Valle de Rio Negro and Neuquen. The aim of the present study was to evaluate the effect of chlorpyrifos on cell proliferation of human breast cancer cell line, MCF-7. Proliferation was evaluated by clonogenic assay andbromodeoxyuridine (BrdU) incorporation; cell viability by MTT assay. Reactive oxygen species (ROS) were determined using DCF fluorescent staining and flow citometry. Protein expression was assessed by Western blot. Our results indicate that high concentrations of chlorpyrifos (50 ìM) decreased 40% clonogenic proliferation and 18% cell viability. The inhibitory effect onproliferation was associated to an increase of 32% in the content of ROS and 48% p27 protein expression. On the other hand, exposure of cells to low concentrations of chlorpyrifos (50 nM) stimulated BrdU incorporation in 88%. This effect was related to an enhanced expression of proliferating cell nuclear antigen (PCNA) and cyclin E. We conclude that chlorpyrifos modulates proliferation in a dose dependent way, increasing proliferation at low doses whiledecreasing it at high concentrations.