Effects of the endocrine disruptors atrazine and PCB 153 on the protein expression of MCF-7 human cells.
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-beta 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.
Department Environment and Agro-Biotechnologies, Centre de Recherche Public - Gabriel Lippmann, L-4422 Belvaux, Luxembourg.
Jean-Paul
JP
Lasserre
Fred
F
Fack
Dominique
D
Revets
Sébastien
S
Planchon
Jenny
J
Renaut
Lucien
L
Hoffmann
Arno C
AC
Gutleb
Claude P
CP
Muller
Torsten
T
Bohn
D001280:Atrazine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D052244:Endocrine Disruptors; D011506:Proteins; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D001280:Atrazine; C014024:2,4,5,2',4',5'-hexachlorobiphenyl