title: Hepatic transcriptomic and metabolomic responses in the stickleback (Gasterosteus aculeatus) exposed to environmentally relevant concentrations of dibenzanthracene.
abstract: A three-spined stickleback (Gasterosteus aculeatus) cDNA array and one-dimensional 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolomics approach, together with individual biomarkers,were employed to investigate the responses of male sticklebacks to polycyclic aromatic hydrocarbon exposure. Fish were exposed to 1,2:5,6-dibenzanthracene (DbA) at concentrations between 0.01 and 50 microg per liter dissolved in the ambient water for four days, and hepatic transcript and metabolite profiles were determined in comparison with those of solvent-exposed controls. Induction of gene expression was apparent for cytochrome P450 1A (CYP1A) and CYP2-family monooxygenases and these responses were strongly correlated with DbA exposure concentrations (for CYP1A r > 0.996). Expression of suites of genes related to bile acid biosynthesis, steroid metabolism, and endocrine function were also affected, as demonstrated by gene ontology analyses. Expression changes in selected genes were confirmed by real-time PCR. Metabolomics highlighted notable changes in concentrations of taurine, malonate, glutamate, and alanine. These statistically significant responses to environmentally relevant concentrations of DbA at the transcriptomic and metabolomic levels provided sensitive markers characteristic of environmentally relevant low-level DbA exposure. Metabolic pathways were identified where both gene expression and metabolite concentrations were altered in response to DbA.
authors.affiliation: School of Biosciences, The University of Birmingham, Birmingham, B15 2TT, UK. t.d.williams@bham.ac.uk
authors.forename: Tim D
authors.initials: TD
authors.lastname: Williams
authors.forename: Huifeng
authors.initials: H
authors.lastname: Wu
authors.forename: Eduarda M
authors.initials: EM
authors.lastname: Santos
authors.forename: Jon
authors.initials: J
authors.lastname: Ball
authors.forename: Ioanna
authors.initials: I
authors.lastname: Katsiadaki
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Brown
authors.forename: Paul
authors.initials: P
authors.lastname: Baker
authors.forename: Fernando
authors.initials: F
authors.lastname: Ortega
authors.forename: Francesco
authors.initials: F
authors.lastname: Falciani
authors.forename: John A
authors.initials: JA
authors.lastname: Craft
authors.forename: Charles R
authors.initials: CR
authors.lastname: Tyler
authors.forename: James K
authors.initials: JK
authors.lastname: Chipman
authors.forename: Mark R
authors.initials: MR
authors.lastname: Viant
mesh_terms: D000818:Animals; D001551:Benz(a)Anthracenes / Q000008:administration & dosage / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects / Q000378:metabolism; D004781:Environmental Exposure / Q000032:analysis; D004784:Environmental Monitoring; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D050216:Metabolic Detoxication, Phase I; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055432:Metabolomics; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D023701:Smegmamorpha / Q000235:genetics* / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism; D018675:Toxicity Tests
chemical_list: D001551:Benz(a)Anthracenes; D013256:Steroids; C016365:dibenzanthracenes