title: Liver transcriptome analysis of Atlantic cod (Gadus morhua) exposed to PCB 153 indicates effects on cell cycle regulation and lipid metabolism.
abstract: BACKGROUND
  Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) with harmful effects in animals and humans. Although PCB 153 is one of the most abundant among PCBs detected in animal tissues, its mechanism of toxicity is not well understood. Only few studies have been conducted to explore genes and pathways affected by PCB 153 by using high throughput transcriptomics approaches. To obtain better insights into toxicity mechanisms, we treated juvenile Atlantic cod (Gadus morhua) with PCB 153 (0.5, 2 and 8 mg/kg body weight) for 2 weeks and performed gene expression analysis in the liver using oligonucleotide arrays.
  
  
  RESULTS
  Whole-genome gene expression analysis detected about 160 differentially regulated genes. Functional enrichment, interactome, network and gene set enrichment analysis of the differentially regulated genes suggested that pathways associated with cell cycle, lipid metabolism, immune response, apoptosis and stress response were among the top significantly enriched. Particularly, genes coding for proteins in DNA replication/cell cycle pathways and enzymes of lipid biosynthesis were up-regulated suggesting increased cell proliferation and lipogenesis, respectively.
  
  
  CONCLUSIONS
  PCB 153 appears to activate cell proliferation and lipogenic genes in cod liver. Transcriptional up-regulation of marker genes for lipid biosynthesis resembles lipogenic effects previously reported for persistent organic pollutants (POPs) and other environmental chemicals. Our results provide new insights into mechanisms of PCB 153 induced toxicity.
authors.affiliation: Department of Molecular Biology, University of Bergen, Bergen, Norway. Fekadu.Yadetie@mbi.uib.no.
authors.forename: Fekadu
authors.initials: F
authors.lastname: Yadetie
authors.forename: Odd André
authors.initials: OA
authors.lastname: Karlsen
authors.forename: Marta
authors.initials: M
authors.lastname: Eide
authors.forename: Christer
authors.initials: C
authors.lastname: Hogstrand
authors.forename: Anders
authors.initials: A
authors.lastname: Goksøyr
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D016000:Cluster Analysis; D019295:Computational Biology; D048389:Gadus morhua / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl