Source:http://linkedlifedata.com/resource/pubmed/id/17532181
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2007-8-16
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pubmed:abstractText |
Interactions of environmental pollutants with the thyroid endocrine axis have received much attention especially because thyroid hormones (THs) play a major role in mammalian brain development. In order to screen for compounds that act on the triiodothyronine (T3) signaling pathway, we developed a new reporter gene assay expressing luciferase under the control of the TH receptor (TR). PC12 cells expressing the alpha1-isoform of TR of avian origin were stably transfected with a luciferase gene controlled by the SV40 promoter, and enhanced by a four-spaced direct repeat (DR4) thyroid response element (TRE). The resulting PC-DR-LUC cells were used to optimize a T3 assay in multiwell microplates. This assay was highly sensitive (30 pM T3) and reproducible, and responded as expected to TH analogues. Several halogenated phenolic (3,3',5,5'-tetrabromobisphenol A, 3,3',5,5'-tetrachlorobisphenol A, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl) and phenol (pentachlorophenol, 2,4,6-triiodophenol) compounds suspected of being thyroid-disrupting environmental chemicals induced partial agonistic and/or complex competitive/uncompetitive antagonistic responses in PC-DR-LUC cells at micromolar concentrations. A cell viability test indicated that these effects were not related to cytotoxicity of the chemicals. These results suggest that the PC-DR-LUC assay could be a valuable tool for the large-scale screening for thyroid receptor agonists and antagonists in vitro, and for detecting thyroid disruptors in the environment.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Endocrine Disruptors,
http://linkedlifedata.com/resource/pubmed/chemical/Environmental Pollutants,
http://linkedlifedata.com/resource/pubmed/chemical/Flame Retardants,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Phenols,
http://linkedlifedata.com/resource/pubmed/chemical/Polybrominated Biphenyls,
http://linkedlifedata.com/resource/pubmed/chemical/Polychlorinated Biphenyls,
http://linkedlifedata.com/resource/pubmed/chemical/Thyroid Hormone Receptors alpha,
http://linkedlifedata.com/resource/pubmed/chemical/tetrabromobisphenol A
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0887-2333
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1197-205
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pubmed:dateRevised |
2009-4-10
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pubmed:meshHeading |
pubmed-meshheading:17532181-Animals,
pubmed-meshheading:17532181-Biological Assay,
pubmed-meshheading:17532181-Endocrine Disruptors,
pubmed-meshheading:17532181-Environmental Pollutants,
pubmed-meshheading:17532181-Flame Retardants,
pubmed-meshheading:17532181-Genes, Reporter,
pubmed-meshheading:17532181-Luciferases,
pubmed-meshheading:17532181-Luminescence,
pubmed-meshheading:17532181-PC12 Cells,
pubmed-meshheading:17532181-Phenols,
pubmed-meshheading:17532181-Polybrominated Biphenyls,
pubmed-meshheading:17532181-Polychlorinated Biphenyls,
pubmed-meshheading:17532181-Rats,
pubmed-meshheading:17532181-Thyroid Hormone Receptors alpha,
pubmed-meshheading:17532181-Transcription, Genetic,
pubmed-meshheading:17532181-Transfection
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pubmed:year |
2007
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pubmed:articleTitle |
A new bioluminescent cellular assay to measure the transcriptional effects of chemicals that modulate the alpha-1 thyroid hormone receptor.
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pubmed:affiliation |
Univ Paris-Sud, Faculté de Pharmacie, Laboratoire Santé Publique-Environnement, F-92296 Châtenay-Malabry, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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