Identifying Health Impacts of Exposure to Copper Using Transcriptomics and Metabolomics in a Fish Model

• Published in: Environmental science & technology 2010-01, Vol.44 (2), p.820-826
• Main Authors: Santos, Eduarda M, Ball, Jonathan S, Williams, Tim D, Wu, Huifeng, Ortega, Fernando, van Aerle, Ronny, Katsiadaki, Ioanna, Falciani, Francesco, Viant, Mark R, Chipman, James K, Tyler, Charles R
• Format: Article
• Language: English
• Subjects: Agnatha. Pisces; Animal, plant and microbial ecology; Animals; Applied ecology; Applied sciences; Aquatic ecosystems; Biochemistry; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Cholesterol - biosynthesis; Copper; Copper - toxicity; DNA Damage - drug effects; Dose-Response Relationship, Drug; Down-Regulation; Ecotoxicology and Human Environmental Health; Ecotoxicology, biological effects of pollution; Effects of pollution and side effects of pesticides on vertebrates; Environmental pollutants toxicology; Environmental science; Exact sciences and technology; Fish; Fundamental and applied biological sciences. Psychology; Gasterosteus aculeatus; Gene expression; Human exposure; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Metals and various inorganic compounds; Pollution; Smegmamorpha; Toxicity; Toxicology; Water; Water Pollutants, Chemical - toxicity
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/es902558k

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 μg 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 μg of Cu/L). Genes associated with the cholesterol biosynthesis pathway were significantly over-represented and consistently down-regulated (at 128 μg 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.