title: Hepatic transcriptomic profiling reveals early toxicological mechanisms of uranium in Atlantic salmon (Salmo salar).
abstract: BACKGROUND
  Uranium (U) is a naturally occurring radionuclide that has been found in the aquatic environment due to anthropogenic activities. Exposure to U may pose risk to aquatic organisms due to its radiological and chemical toxicity. The present study aimed to characterize the chemical toxicity of U in Atlantic salmon (Salmo salar) using depleted uranium (DU) as a test model. The fish were exposed to three environmentally relevant concentrations of DU (0.25, 0.5 and 1.0 mg U/L) for 48 h. Hepatic transcriptional responses were studied using microarrays in combination with quantitative real-time reverse transcription polymerase chain reaction (qPCR). Plasma variables and chromosomal damages were also studied to link transcriptional responses to potential physiological changes at higher levels.
  
  
  RESULTS
  The microarray gene expression analysis identified 847, 891 and 766 differentially expressed genes (DEGs) in the liver of salmon after 48 h exposure to 0.25, 0.5 and 1.0 mg/L DU, respectively. These DEGs were associated with known gene ontology functions such as generation of precursor metabolites and energy, carbohydrate metabolic process and cellular homeostasis. The salmon DEGs were then mapped to mammalian orthologs and subjected to protein-protein network and pathway analysis. The results showed that various toxicity pathways involved in mitochondrial functions, oxidative stress, nuclear receptor signaling, organ damage were commonly affected by all DU concentrations. Eight genes representative of several key pathways were further verified using qPCR No significant formation of micronuclei in the red blood cells or alterations of plasma stress variables were identified.
  
  
  CONCLUSIONS
  The current study suggested that the mitochondrion may be a key target of U chemical toxicity in salmon. The induction of oxidative stress and uncoupling of oxidative phosphorylation may be two potential modes of action (MoA) of DU. These MoAs may subsequently lead to downstream events such as apoptosis, DNA repair, hypoxia signaling and immune response. The early toxicological mechanisms of U chemical toxicity in salmon has for the first time been systematically profiled. However, no other physiological changes were observed. Future efforts to link transcriptional responses to adverse effects have been outlined as important for understanding of potential risk to aquatic organisms.
authors.affiliation: Department of Environmental Sciences (IMV), Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Centre for Environmental Radioactivity (CERAD), P,O, Box 5003, N-1432 Ås, Norway. yso@niva.no.
authors.forename: You
authors.initials: Y
authors.lastname: Song
authors.forename: Brit
authors.initials: B
authors.lastname: Salbu
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Teien
authors.forename: Lene
authors.initials: L
authors.lastname: Sørlie Heier
authors.forename: Bjørn Olav
authors.initials: BO
authors.lastname: Rosseland
authors.forename: Tore
authors.initials: T
authors.lastname: Høgåsen
authors.forename: Knut Erik
authors.initials: KE
authors.lastname: Tollefsen
mesh_terms: D000818:Animals; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053858:Metabolic Networks and Pathways; D048629:Micronuclei, Chromosome-Defective; D020317:Salmo salar / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects*; D014501:Uranium / Q000633:toxicity*; D014875:Water Pollutants, Radioactive / Q000633:toxicity*
chemical_list: D029941:Fish Proteins; D014875:Water Pollutants, Radioactive; D014501:Uranium