Submitted to: Biochemical and Biophysical Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/1/2004
Publication Date: 7/1/2004
Citation: Koskinen, H., Pehkonen, P., Vehniainen, E., Krasnov, A., Rexroad III, C.E., Afanasyev, S., Molsa, H., Oikari, A. 2004. Response of rainbow trout transcriptome to model chemical contaminants. Biochemical and Biophysical Research Communications. 320(3):745-753.
Interpretive Summary: The goal of this study was to evaluate the usefulness of microarray technology in characterizing rainbow trout responses to toxic compounds. Merging this new high-throughput analytic technology with bioinformatics is referred to as a novel scientific discipline, toxicogenomics. Yolk-sac fry were exposed short-term to sublethal doses of four toxic chemicals, representing a ligand acting through the aryl hydrocarbon receptor (AhR), a non-essential heavy metal, an industrial chlorinated solvent, and an environmentally relevant polycyclic aromatic hydrocarbon (PAH). Utilizing a 1300 gene cDNA microarray we characterized the effects of different chemicals on gene expression, identified potential diagnostic biomarkers, and gained further understanding of molecular mechanisms responding to toxicity.
Technical Abstract: We used high-density glass cDNA microarray for studies of genomic response in yolk-sac fry of rainbow trout to sublethal range of model waterborne contaminants (ß'naphthoflavone, cadmium, carbon tetrachloride and pyrene). For development of diagnostic biomarkers, we selected one up-regulated and one down-regulated gene for each toxic compound and their differential expression was verified with real-time qRT PCR. To address molecular mechanisms of toxicity, the differentially expressed genes were grouped by the functional categories of Gene Ontology and a number of classes showed significantly different response to the studied compounds. Responses were related to cell cycle, apoptosis, signal transduction, oxidative stress, subcellular and extracellular structures, protein biosynthesis and modification, enzymes and various metabolic pathways. Rainbow trout showed distinct genomic response to low and medium doses of the contaminants, whereas at high levels the adaptive reactions were masked with general unspecific response to toxicity. We found enhanced expression of many mitochondrial proteins and genes involved in metabolism of metal ions and protein biosynthesis. In parallel, genes related to stress and immune response, signal transduction and nucleotide metabolism were down-regulated. To facilitate interpretation of results, we performed computer-assisted analyses of Medline abstracts retrieved for each compound, which helped to indicate the expected and novel findings.