title: Transcriptional profiles induced by the Aryl Hydrocarbon Receptor agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8-pentachlorodibenzofuran in primary rat hepatocytes.
abstract: Toxicogenomics was used to examine mRNA expression profiles obtained from primary rat hepatocytes treated for 24h with 0.01 or 1.0 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), 0.02 or 2.0 nM 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF) and 0.1 or 10nM 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF). The concentrations of 2,3,4,7,8-PeCDF and 2,3,7,8-TCDF were chosen to be equivalent to 2,3,7,8-TCDD's concentration based on the toxic equivalency factor/toxic equivalent (TEF/TEQ) method for estimating biological potency. 2,3,7,8-TCDD at 1.0 nM altered the expression of 533 genes; 2,3,4,7,8-PeCDF at 2.0 nM altered 182 genes, and 2,3,7,8-TCDF at 10nM altered 154 genes. Of these, 57 genes were affected by all three congeners. Agglomerative hierarchical clustering revealed distinct congener-dependent gene subclusters. Principal components analyses of the microarray data revealed that these congeners cluster independently of one another. Data presented here demonstrate that equivalent TEQ concentrations of 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF and 2,3,7,8-TCDF, while altering the expression of a small battery of genes in common, also produce substantial congener specific alterations in gene expression.
authors: The Dow Chemical Company, Toxicology and Environmental Research & Consulting, 1803 Bldg., Washington Street, Midland, MI 48674, United States. jcrowlands@dow.com
authors: J Craig
authors: JC
authors: Rowlands
authors: Robert
authors: R
authors: Budinsky
authors: Bhaskar
authors: B
authors: Gollapudi
authors: Raymond
authors: R
authors: Novak
authors: Mohamed
authors: M
authors: Abdelmegeed
authors: Daniela
authors: D
authors: Cukovic
authors: Alan
authors: A
authors: Dombkowski
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects*; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D025341:Principal Component Analysis; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists*
chemical_list: D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C038890:2,3,4,7,8-pentachlorodibenzofuran; C014211:2,3,7,8-tetrachlorodibenzofuran