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Abstract
Copper (Cu) is a micronutrient essential for the biochemical functioning of numerous processes in vertebrates but is also often present in the aquatic environment at concentrations able to cause adverse health effects in aquatic organisms. This study investigated the signaling pathways mediating the effects of exposure to Cu using a toxicogenomic approach in a fish model, the stickleback ( Gasterosteus aculeatus ). Freshwater-acclimated male fish were exposed via the water to Cu, including at environmentally relevant concentrations (3.2-128 mug of Cu/L for 4 days), and the biological responses explored through analyses of the hepatic transcriptome and metabolome and phenotypic end points, including assessment of DNA damage in blood cells. The Cu exposures resulted in DNA strand breaks in blood cells at all exposure concentrations and alterations in hepatic gene expression and metabolite concentrations in a concentration-dependent manner (from 10 mug of Cu/L). Genes associated with the cholesterol biosynthesis pathway were significantly over-represented and consistently down-regulated (at 128 mug of Cu/L), similar to that occurring in a mouse model for Wilson's disease. Additionally, inductions in metallothionein and catalase were also observed. The concentrations of NAD(+) and lactate increased significantly with the Cu exposure, consistent with a shift toward anaerobic metabolism, and these aligned closely with changes observed in gene expression. The pathways of Cu toxicity identified in our study support the conserved mechanisms of Cu toxicity from lower vertebrates to mammals, provide novel insights into the deleterious effects of Cu in fish, and further demonstrate the utility of fish as environmental sentinels for chemical impacts on both environmental and human health.
Original language | English |
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Pages (from-to) | 820-826 |
Number of pages | 7 |
Journal | Environmental Science & Technology |
Volume | 44 |
Issue number | 2 |
Early online date | 18 Dec 2009 |
DOIs | |
Publication status | Published - 2010 |
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Dive into the research topics of 'Identifying Health Impacts of Exposure to Copper Using Transcriptomics and Metabolomics in a Fish Model'. Together they form a unique fingerprint.Projects
- 2 Finished
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Identifying and Defining the Bases of Individual and Population Susceptibility and Adaption to Environmental Pollutants in Fish: An Integrated Transcriptomic and Metabolomic Approach
Chipman, K. (Principal Investigator), Falciani, F. (Co-Investigator), Viant, M. (Co-Investigator) & Minchin, S. (Co-Investigator)
Natural Environment Research Council
1/04/05 → 30/11/08
Project: Research Councils
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Fellowship: Dr M.R. Viant: Development of a Predictive Biomarker Model for the Marine and Estuarine Environments using state-of-the-art NMR-based Metabonomics and Bioinformatic Techniques
Viant, M. (Principal Investigator)
Natural Environment Research Council
1/11/03 → 6/01/09
Project: Research Councils