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Effects of the Endocrine Disruptors Atrazine and PCB 153 on the Protein Expression of MCF-7 Human Cells

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Centre de Recherche Public - Gabriel Lippmann, Department Environment and Agro-Biotechnologies, 41, rue du Brill, L-4422 Belvaux, Luxembourg, and Institute of Immunology, National Health Laboratory/CRP-Santé, 20A, rue Auguste Lumière, L-1950 Luxembourg, Luxembourg
* To whom correspondence should be addressed. Torsten Bohn, Centre de Recherche Public - Gabriel Lippmann. E-mail: [email protected]. Phone: (+352)470261480. Fax: (+352) 47 02 64.
†Centre de Recherche Public - Gabriel Lippmann.
‡Institute of Immunology, National Public Health Laboratory.
Cite this: J. Proteome Res. 2009, 8, 12, 5485–5496
Publication Date (Web):September 25, 2009
https://doi.org/10.1021/pr900480f
Copyright © 2009 American Chemical Society
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Abstract

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Polychlorinated biphenyls (PCBs) and a number of pesticides can act as endocrine disrupting compounds (EDCs). These molecules exhibit hormonal activity in vivo, and can therefore interact and perturb normal physiological functions. Many of these compounds are persistent in the environment, and their bioaccumulation may constitute a significant threat for human health.

Physiological abnormalities following exposure to these xenobiotic compounds go along with alterations at the protein level of individual cells. In this study, MCF-7 cells were exposed to environmentally relevant concentrations of atrazine, PCB153 (100 ppb, respectively), 17-β estradiol (positive control, 10 nM) and a negative control (solvent) for t = 24 h (n = 3 replicates/exposure group). After trizol extraction and protein solubilization, protein expression levels were studied by 2D-DIGE. Proteins differentially expressed were excised, trypsin-digested, and identified by MALDI-ToF-ToF, followed by NCBInr database search. 2D-DIGE experiments demonstrated that 49 spots corresponding to 29 proteins were significantly differentially expressed in MCF-7 cells (>1.5-fold, P < 0.05, Student’s paired t test). These proteins belonged to various cellular compartments (nucleus, cytosol, membrane), and varied in function; 88% of proteins were down-regulated during atrazine exposure, whereas 75% of proteins were up-regulated by PCB153. Affected proteins included those regulating oxidative stress such as superoxide dismutase and structural proteins such as actin or tropomyosin, which may explain morphological changes of cells already observed under the microscope. This study highlights the susceptibility of human cells to compounds with endocrine disrupting properties.

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