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Effects of tris(1,3-dichloro-2-propyl) phosphate and tris(1-chloropropyl) phosphate on cytotoxicity and mRNA expression in primary cultures of avian hepatocytes and neuronal cells.
MedLine Citation:
PMID:  22268003     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tris(1-chloropropyl) phosphate (TCPP) belong to a group of chemicals collectively known as triester organophosphate flame retardants (OPFRs). OPFRs are used in a wide range of consumer products and have been detected in biota, including free-living avian species; however, data on toxicological and molecular effects of exposure are limited. An in vitro screening approach was used to compare concentration-dependent effects of TDCPP and TCPP on cytotoxicity and mRNA expression in cultured hepatocytes and neuronal cells derived from embryonic chickens. TDCPP was toxic to hepatocytes (LC50 = 60.3 ± 45.8 μM) and neuronal cells (LC50 = 28.7 ± 19.1 μM) while TCPP did not affect viability in either cell type up to the highest concentration administered; 300 μM. Real-time RT-PCR revealed alterations in mRNA abundance of genes associated with phase I and II metabolism, the thyroid hormone pathway, lipid regulation and growth in hepatocytes. None of the transcripts measured in neuronal cells (D2, D3, RC3 and Oct-1) varied in response to TDCPP or TCPP exposure. Exposure to ≥ 10 μM TDCPP and TCPP resulted in significant up-regulation of CYP2H1 (4- to 8-fold), CYP3A37 (13- to 127-fold) and UGT1A9 (3.5- to 7-fold) mRNA levels. Transthyretin was significantly down-regulated >2-fold by TCPP at 100 μM; however, TDCPP did not alter its expression. Liver fatty acid binding protein, thyroid hormone-responsive spot 14-α, and insulin-like growth factor 1 were all down-regulated (up to 10-fold) in hepatocytes exposed to ≥ 0.01 μM TDCPP and TCPP. Taken together, our results indicate that genes associated with xenobiotic metabolism, the thyroid hormone pathway, lipid regulation, and growth are vulnerable to TDCPP and TCPP administration in cultured avian hepatocytes. The mRNA expression data were similar to those from a previous study with hexabromocyclododecane.
Authors:
Doug Crump; Suzanne Chiu; Sean W Kennedy
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  -     ISSN:  1096-0929     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Environment Canada, National Wildlife Research Centre, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1A 0H3; doug.crump@ec.gc.ca.
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