Sammendrag
In the environment, contaminants typically occur as a complex mixture resulting in a situation whereby certain chemicals may have either synergistic or antagonistic effects upon the toxicological action of another contaminant. The interaction of multiple chemicals with the ER suggests a complex interplay between environmental signals and biological systems. These complex interplays between environmental chemicals with different modes of action have been a subject for systematic investigations in our laboratory. Herein, we report the development of a toxicogenomic tool (SalArray chip) and interactions between an estrogen receptor agonist (nonylphenol) and aryl hydrocarbon receptor agonist (PCB-77), with documented anti-estrogenic effect, using an in vitro based technique. Our data show a biological pathway-dependent differential gene expression patterns after exposure to nonylphenol and PCB-77 using SalArray gene chip. A quantitative evaluation using real-time PCR for vitellogenin (Vtg) and estrogen receptor (ERa) showed that PCB-77 inhibited nonyphenol-induced Vtg and ERa gene expression patterns in trout hepatocytes. PCB-77 induced CYP1A1 gene expression, and partially affected AhR isoforms gene expression. This interaction between two different classes of ligand-activated receptors provides novel mechanistic insights on signaling pathways, with potential deleterial consequences for fish reproduction, development and general health.
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