title: Cytochrome P4501A induction in primary cultures of embryonic European starling hepatocytes exposed to TCDD, PeCDF and TCDF.
abstract: Novel methods that predict the sensitivity of avian embryos to the toxic effects of dioxin-like compounds (DLCs) using either (1) knowledge of the identity of amino acids at key sites within the ligand binding domain of aryl hydrocarbon receptor 1 (AHR1) or (2) a luciferase reporter gene assay that measures AHR1 activation were recently reported. Results from both methods predict that European starling (Sturnus vulgaris) and domestic chicken (Gallus gallus domesticus) embryos have similar sensitivity to the biochemical and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,3,7,8-tetrachlorodibenzofuran (TCDF). Chicken embryos are highly sensitive to DLC toxicity, and the prediction that starlings are equally sensitive is surprising given their widespread distribution and large population size. In an attempt to learn more about starling sensitivity to DLCs, we determined concentration-dependent effects of TCDD, PeCDF and TCDF on cytochrome P4501A4 and 1A5 (CYP1A4 and 1A5) mRNA levels in primary cultures of hepatocytes prepared from embryonic European starlings. It has been demonstrated that the sensitivity of avian hepatocytes to CYP1A4/5 induction is well correlated with LD50 values of DLCs for several avian species. The results of the present study indicate that European starling hepatocytes are indeed as sensitive as chicken hepatocytes to CYP1A4/5 induction after exposure to TCDD. However, starling hepatocytes are less sensitive than chicken hepatocytes to CYP1A4/5 induction by PeCDF and TCDF.
authors.affiliation: Centre for Advanced Research in Environmental Genomics Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Farmahin
authors.forename: Doug
authors.initials: D
authors.lastname: Crump
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Jones
authors.forename: Lukas J
authors.initials: LJ
authors.lastname: Mundy
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D001572:Benzofurans / Q000633:toxicity*; D002470:Cell Survival; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D017930:Genes, Reporter; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007928:Lethal Dose 50; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D018570:Risk Assessment; D046749:Starlings / Q000196:embryology*
chemical_list: D030161:Avian Proteins; D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D008156:Luciferases; D001189:Aryl Hydrocarbon Hydroxylases; C416342:CYP1A4 protein, Gallus gallus; C108015:cytochrome P-450 CYP1A5; C038890:2,3,4,7,8-pentachlorodibenzofuran; C014211:2,3,7,8-tetrachlorodibenzofuran