ToxSci Advance Access published online on December 15, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm293
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Gene expression profiles in rainbow trout, Onchorynchus mykiss, exposed to a simple chemical mixture
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* Battelle, Marine Research Operations, West Sequim Bay Road, Sequim, Washington 98382, sharon.hook{at}pnl.gov, irv.schultz{at}pnl.gov
Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, jack.small{at}pnl.gov
# Current address: Genomic Medicine Institute, Cleveland Clinic (NE50), 9500 Euclid Avenue, Cleveland, Ohio 44195, Phone: (216) 444-8745, Fax: (216) 636-0009, Email: gopalab{at}ccf.org
Corresponding author Phone: 360/681-3626, Fax: 360/681-4559
Received April 20, 2007; revision received October 18, 2007; accepted October 27, 2007
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Abstract |
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Among proposed uses for microarrays in environmental toxiciology is the identification of key contributors to toxicity within a mixture. However, it remains uncertain whether the transcriptomic profiles resulting from exposure to a mixture have patterns of altered gene expression that contain identifiable contributions from each toxicant component. We exposed isogenic rainbow trout Onchorynchus mykiss, to sublethal levels of ethynylestradiol, 2,2,4,4 tetrabromodiphenyl ether, and chromium VI or to a mixture of all three toxicants Fluorescently labeled cDNA were generated and hybridized against a commercially available Salmonid array spotted with 16,000 cDNAs. Data were analyzed using ANOVA (p < 0.05) with a Benjamani-Hochberg multiple test correction (Genespring (Agilent) software package) to identify up and down regulated genes. Gene clustering patterns that can be used as "expression signatures" were determined using hierarchical cluster analysis. The gene ontology terms associated with significantly altered genes were also used to identify functional groups that were associated with toxicant exposure. Cross-ontological analytics (XOA) approach was used to assign functional annotations to genes with "unknown" function. Our analysis indicates that transcriptomic profiles resulting from the mixture exposure resemble those of the individual contaminant exposures, but are not a simple additive list. However, patterns of altered genes representative of each component of the mixture are clearly discernible, and the functional classes of genes altered represent the individual components of the mixture. These findings indicate that the use of microarrays to identify transcriptomic profiles may aid in the identification of key stressors within a chemical mixture, ultimately improving environmental assessment
Key Words: Gene expression; microarrays; chemical mixtures; rainbow trout; toxicokinetics.