title: Gene expression profiles in fathead minnow exposed to 2,4-DNT: correlation with toxicity in mammals.
abstract: Toxicogenomics, the genome-wide analysis of gene expression to study the effect of toxicants, has great potential for use in environmental toxicology. Applied to standard test organisms, it has possible applications in aquatic toxicology as a sensitive monitoring tool to detect the presence of contaminants while providing information on the mechanisms of action of these pollutants. We describe the use of a complementary DNA (cDNA) microarray of the fathead minnow (Pimephales promelas) a standard sentinel organism in aquatic toxicology, to better understand the mechanisms of toxicity of 2,4-dinitrotoluene (2,4-DNT) which is released in the environment through military and industrial use. We have constructed a fathead minnow microarray containing 5000 randomly picked anonymous cDNAs from a whole fish cDNA library. Expression profiles were analyzed in fish exposed to 2,4-DNT for 10 days at three concentrations (11, 22, and 44 microM, respectively) below the measured median lethal concentration (58 microM). Sequence analysis of cDNAs corresponding to differentially expressed genes affected by exposure revealed that lipid metabolism and oxygen transport genes were prominently affected in a dose-specific manner. We measured liver lipids and demonstrate that lipid metabolism is indeed perturbed following exposure. These observations correlate well with available toxicological data on 2,4-DNT. We present possible modes of action of 2,4-DNT toxicity and suggest that fathead minnow cDNA microarrays can be useful to identify mechanisms of toxicity in fish and as a predictive tool for toxicity in mammals.
authors.affiliation: Department of Nutritional Sciences and Toxicology, Morgan Hall and Berkeley Institute of the Environment, University of California, Berkeley, California 94720, USA. wintz@berkeley.edu
authors.forename: Henri
authors.initials: H
authors.lastname: Wintz
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Yoo
authors.forename: Alex
authors.initials: A
authors.lastname: Loguinov
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Steevens
authors.forename: Ricky D
authors.initials: RD
authors.lastname: Holland
authors.forename: Richard D
authors.initials: RD
authors.lastname: Beger
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Perkins
authors.forename: Owen
authors.initials: O
authors.lastname: Hughes
authors.forename: Chris D
authors.initials: CD
authors.lastname: Vulpe
mesh_terms: D000818:Animals; D044926:Butyryl-CoA Dehydrogenase / Q000235:genetics; D003530:Cyprinidae / Q000235:genetics* / Q000378:metabolism; D004136:Dinitrobenzenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004784:Environmental Monitoring / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D047493:PPAR alpha / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D010743:Phospholipids / Q000032:analysis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D004136:Dinitrobenzenes; D051557:Hepatocyte Nuclear Factor 4; D047493:PPAR alpha; D047495:PPAR gamma; D010743:Phospholipids; C016403:2,4-dinitrotoluene; D044926:Butyryl-CoA Dehydrogenase