title: Early stress responses in Atlantic salmon (Salmo salar) exposed to environmentally relevant concentrations of uranium.
abstract: Uranium (U) is a naturally occurring heavy metal widely used in many military and civil applications. Uranium contamination and the associated potential adverse effects of U on the aquatic environment have been debated during recent years. In order to understand the effect and mode of action (MoA) of U in vivo, juvenile Atlantic salmon (Salmo salar) were exposed to 0.25 mg/L, 0.5 mg/L and 1.0mg/L waterborne depleted uranyl acetate, respectively, in a static system for 48 h. The U concentrations in the gill and liver were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and the resulting biological effects were determined by a combination of analysis of gene expression and micronuclei formation. The hepatic transcriptional level of 12 biomarker genes from four stress-response categories, including oxidative stress (γ-glutamyl cysteine synthetase (GCS), glutathione reductase (GR), glutathione peroxidase (GPx)), DNA damage and repair (P53, cyclin-dependent kinase inhibitor 1 (P21), growth arrest and DNA damage-inducible gene gamma (Gadd45G), proliferating cell nuclear antigen (PCNA), Rad51), apoptosis (Bcl2-associated X protein (BAX), Bcl-x, Caspase 6A,) and protein degradation (Ubiquitin) were evaluated by quantitative real-time polymerase chain reaction (q-rtPCR). The results clearly showed accumulation of U in the gill and liver with increasing concentrations of U in the exposure water. The effects of U on differential hepatic gene expression also occurred in a concentration-dependent manner, although deviations from ideal concentration-response relationships were observed at the highest U concentration (1.0 mg/L). All the genes tested were found to be up-regulated by U while no significant micronuclei formation was identified. The results suggest that U may cause oxidative stress in fish liver at concentrations greater than 0.25 mg/L, giving rise to clear induction of several toxicologically relevant biomarker genes, although no significant adverse effects were observed after the relatively short exposure period.
authors.affiliation: Norwegian University of Life Sciences-UMB, Department of Plant and Environmental Sciences. P.O. Box 5003, N-1432 Ås, Norway. you.song@umb.no
authors.forename: You
authors.initials: Y
authors.lastname: Song
authors.forename: Brit
authors.initials: B
authors.lastname: Salbu
authors.forename: Lene Sørlie
authors.initials: LS
authors.lastname: Heier
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Teien
authors.forename: Ole-Christian
authors.initials: OC
authors.lastname: Lind
authors.forename: Deborah
authors.initials: D
authors.lastname: Oughton
authors.forename: Karina
authors.initials: K
authors.lastname: Petersen
authors.forename: Bjørn Olav
authors.initials: BO
authors.lastname: Rosseland
authors.forename: Lindis
authors.initials: L
authors.lastname: Skipperud
authors.forename: Knut Erik
authors.initials: KE
authors.lastname: Tollefsen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects; D020317:Salmo salar / Q000502:physiology*; D012623:Seawater / Q000737:chemistry; D013312:Stress, Physiological / Q000187:drug effects*; D014501:Uranium / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D014874:Water Pollutants, Chemical; D014501:Uranium