PMID- 21609454 OWN - NLM STAT- MEDLINE DCOM- 20110926 LR - 20211020 IS - 1471-2164 (Electronic) IS - 1471-2164 (Linking) VI - 12 DP - 2011 May 24 TI - Transcriptomic assessment of resistance to effects of an aryl hydrocarbon receptor (AHR) agonist in embryos of Atlantic killifish (Fundulus heteroclitus) from a marine Superfund site. PG - 263 LID - 10.1186/1471-2164-12-263 [doi] AB - BACKGROUND: Populations of Atlantic killifish (Fundulus heteroclitus) have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs) and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR)-dependent signaling pathway. The resistance is accompanied by reduced sensitivity to induction of cytochrome P450 1A (CYP1A), a widely used biomarker of aromatic hydrocarbon exposure and effect, but whether the reduced sensitivity is specific to CYP1A or reflects a genome-wide reduction in responsiveness to all AHR-mediated changes in gene expression is unknown. We compared gene expression profiles and the response to 3,3',4,4',5-pentachlorobiphenyl (PCB-126) exposure in embryos (5 and 10 dpf) and larvae (15 dpf) from F. heteroclitus populations inhabiting the New Bedford Harbor, Massachusetts (NBH) Superfund site (PCB-resistant) and a reference site, Scorton Creek, Massachusetts (SC; PCB-sensitive). RESULTS: Analysis using a 7,000-gene cDNA array revealed striking differences in responsiveness to PCB-126 between the populations; the differences occur at all three stages examined. There was a sizeable set of PCB-responsive genes in the sensitive SC population, a much smaller set of PCB-responsive genes in NBH fish, and few similarities in PCB-responsive genes between the two populations. Most of the array results were confirmed, and additional PCB-regulated genes identified, by RNA-Seq (deep pyrosequencing). CONCLUSIONS: The results suggest that NBH fish possess a gene regulatory defect that is not specific to one target gene such as CYP1A but rather lies in a regulatory pathway that controls the transcriptional response of multiple genes to PCB exposure. The results are consistent with genome-wide disruption of AHR-dependent signaling in NBH fish. FAU - Oleksiak, Marjorie F AU - Oleksiak MF AD - Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. FAU - Karchner, Sibel I AU - Karchner SI FAU - Jenny, Matthew J AU - Jenny MJ FAU - Franks, Diana G AU - Franks DG FAU - Welch, David B Mark AU - Welch DB FAU - Hahn, Mark E AU - Hahn ME LA - eng GR - P42 ES007381/ES/NIEHS NIH HHS/United States GR - P42ES007381/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110524 PL - England TA - BMC Genomics JT - BMC genomics JID - 100965258 RN - 0 (Receptors, Aryl Hydrocarbon) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases) RN - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl) SB - IM MH - Animals MH - Aryl Hydrocarbon Hydroxylases/biosynthesis MH - Drug Resistance/*genetics MH - Embryo, Nonmammalian/*drug effects/*metabolism MH - Enzyme Induction/drug effects/genetics MH - Fundulidae/*embryology/*genetics MH - *Gene Expression Profiling MH - Genome/genetics MH - High-Throughput Nucleotide Sequencing MH - Larva/drug effects/genetics MH - Oceans and Seas MH - Oligonucleotide Array Sequence Analysis MH - Polychlorinated Biphenyls/toxicity MH - Receptors, Aryl Hydrocarbon/*agonists MH - Sequence Analysis, RNA MH - Time Factors PMC - PMC3213123 EDAT- 2011/05/26 06:00 MHDA- 2011/09/29 06:00 PMCR- 2011/05/24 CRDT- 2011/05/26 06:00 PHST- 2011/01/26 00:00 [received] PHST- 2011/05/24 00:00 [accepted] PHST- 2011/05/26 06:00 [entrez] PHST- 2011/05/26 06:00 [pubmed] PHST- 2011/09/29 06:00 [medline] PHST- 2011/05/24 00:00 [pmc-release] AID - 1471-2164-12-263 [pii] AID - 10.1186/1471-2164-12-263 [doi] PST - epublish SO - BMC Genomics. 2011 May 24;12:263. doi: 10.1186/1471-2164-12-263.