Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

•First study on early stress responses in salmon exposed to low-dose gamma radiation.•Dramatic dose-dependent transcriptional responses characterized.•Multiple modes of action proposed for gamma radiation. Due to the production of free radicals, gamma radiation may pose a hazard to living organisms....

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Bibliographic Details
Published in:	Aquatic toxicology 2014-11, Vol.156, p.52-64
Main Authors:	Song, You, Salbu, Brit, Teien, Hans-Christian, Heier, Lene Sørlie, Rosseland, Bjørn Olav, Tollefsen, Knut Erik
Format:	Article
Language:	eng
Subjects:	Animals Atlantic salmon Biological and medical sciences Biological effects of radiation Biomarkers - metabolism DNA Damage - radiation effects Fundamental and applied biological sciences. Psychology Gamma radiation Gamma Rays Gene expression Gene Expression Profiling Gene Expression Regulation - radiation effects Ionizing radiations Liver - radiation effects Marine Microarray Mode of action Oxidative Stress - radiation effects Pathway Radioactive Pollutants - toxicity Real-Time Polymerase Chain Reaction Salmo salar Salmo salar - genetics Salmo salar - metabolism Tissues, organs and organisms biophysics Water Pollutants, Chemical - toxicity
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Summary:	•First study on early stress responses in salmon exposed to low-dose gamma radiation.•Dramatic dose-dependent transcriptional responses characterized.•Multiple modes of action proposed for gamma radiation. Due to the production of free radicals, gamma radiation may pose a hazard to living organisms. The high-dose radiation effects have been extensively studied, whereas the ecotoxicity data on low-dose gamma radiation is still limited. The present study was therefore performed using Atlantic salmon (Salmo salar) to characterize effects of low-dose (15, 70 and 280mGy) gamma radiation after short-term (48h) exposure. Global transcriptional changes were studied using a combination of high-density oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (qPCR). Differentially expressed genes (DEGs; in this article the phrase gene expression is taken as a synonym of gene transcription, although it is acknowledged that gene expression can also be regulated, e.g., at protein stability and translational level) were determined and linked to their biological meanings predicted using both Gene Ontology (GO) and mammalian ortholog-based functional analyses. The plasma glucose level was also measured as a general stress biomarker at the organism level. Results from the microarray analysis revealed a dose-dependent pattern of global transcriptional responses, with 222, 495 and 909 DEGs regulated by 15, 70 and 280mGy gamma radiation, respectively. Among these DEGs, only 34 were commonly regulated by all radiation doses, whereas the majority of differences were dose-specific. No GO functions were identified at low or medium doses, but repression of DEGs associated with GO functions such as DNA replication, cell cycle regulation and response to reactive oxygen species (ROS) were observed after 280mGy gamma exposure. Ortholog-based toxicity pathway analysis further showed that 15mGy radiation affected DEGs associated with cellular signaling and immune response; 70mGy radiation affected cell cycle regulation and DNA damage repair, cellular energy production; and 280mGy radiation affected pathways related to cell cycle regulation and DNA repair, mitochondrial dysfunction and immune functions. Twelve genes representative of key pathways found in this study were verified by qPCR. Potential common MoAs of low-dose gamma radiation may include induction of oxidative stress, DNA damage and disturbance of oxidative phosphorylation (OXPHOS
ISSN:	0166-445X 1879-1514