Toxicological Sciences 67, 219-231 (2002)
Copyright © 2002 by the Society of Toxicology
MOLECULAR AND GENETIC TOXICOLOGY |
Gene Expression Analysis Reveals Chemical-Specific Profiles
* National Institute of Environmental Health Sciences, P.O. Box 12233, MD2-04, Research Triangle Park, North Carolina 27709; and
Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877
The application of gene expression profiling technology to examine multiple genes and signaling pathways simultaneously promises a significant advance in understanding toxic mechanisms to ultimately aid in protection of public health. Public and private efforts in the new field of toxicogenomics are focused on populating databases with gene expression profiles of compounds where toxicological and pathological endpoints are well characterized. The validity and utility of a toxicogenomics is dependent on whether gene expression profiles that correspond to different chemicals can be distinguished. The principal hypothesis underlying a toxicogenomic or pharmacogenomic strategy is that chemical-specific patterns of altered gene expression will be revealed using high-density microarray analysis of tissues from exposed organisms. Analyses of these patterns should allow classification of toxicants and provide important mechanistic insights. This report provides a verification of this hypothesis. Patterns of gene expression corresponding to liver tissue derived from chemically exposed rats revealed similarity in gene expression profiles between animals treated with different agents from a common class of compounds, peroxisome proliferators [clofibrate (ethyl-p-chlorophenoxyisobutyrate), Wyeth 14,643 ([4-chloro-6(2,3-xylidino)-2-pyrimidinylthio]acetic acid), and gemfibrozil (5-2[2,5-dimethylphenoxy]2-2-dimethylpentanoic acid)], but a very distinct gene expression profile was produced using a compound from another class, enzyme inducers (phenobarbital).
Key Words: gene expression; toxicogenomics; DNA arrays; classification; rat liver; pattern recognition.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S.-B. Kwon, J.-S. Park, J.-Y. Yi, J.-W. Hwang, M. Kim, M.-O. Lee, B.-H. Lee, H.-L. Kim, J. H. Kim, H. Chung, et al. Time- and Dose-based Gene Expression Profiles Produced by a Bile-duct-damaging Chemical, 4,4'-methylene Dianiline, in Mouse Liver in an Acute Phase Toxicol Pathol, July 1, 2008; 36(5): 660 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N'Jai, D. R. Boverhof, E. Dere, L. D. Burgoon, Y. S. Tan, J. C. Rowlands, R. A. Budinsky, K. E. Stebbins, and T. R. Zacharewski Comparative Temporal Toxicogenomic Analysis of TCDD- and TCDF-Mediated Hepatic Effects in Immature Female C57BL/6 Mice Toxicol. Sci., June 1, 2008; 103(2): 285 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Benninghoff and D. E. Williams Identification of a Transcriptional Fingerprint of Estrogen Exposure in Rainbow Trout Liver Toxicol. Sci., January 1, 2008; 101(1): 65 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Zidek, J. Hellmann, P.-J. Kramer, and P. G. Hewitt Acute Hepatotoxicity: A Predictive Model Based on Focused Illumina Microarrays Toxicol. Sci., September 1, 2007; 99(1): 289 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Beyer, R. C. Fry, M. R. Lasarev, L. A. McConnachie, L. B. Meira, V. S. Palmer, C. L. Powell, P. K. Ross, T. K. Bammler, B. U. Bradford, et al. Multicenter Study of Acetaminophen Hepatotoxicity Reveals the Importance of Biological Endpoints in Genomic Analyses Toxicol. Sci., September 1, 2007; 99(1): 326 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Woods, J. P. Vanden Heuvel, and I. Rusyn Genomic Profiling in Nuclear Receptor-Mediated Toxicity Toxicol Pathol, June 1, 2007; 35(4): 474 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Cornwell and R. G. Ulrich Investigating the Mechanistic Basis for Hepatic Toxicity Induced by an Experimental Chemokine Receptor 5 (CCR5) Antagonist Using a Compendium of Gene Expression Profiles Toxicol Pathol, June 1, 2007; 35(4): 576 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rokushima, K. Omi, A. Araki, Y. Kyokawa, N. Furukawa, F. Itoh, K. Imura, K. Takeuchi, M. Okada, I. Kato, et al. A Toxicogenomic Approach Revealed Hepatic Gene Expression Changes Mechanistically Linked to Drug-Induced Hemolytic Anemia Toxicol. Sci., February 1, 2007; 95(2): 474 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Kienhuis, H. M. Wortelboer, J.-C. Hoflack, E. J. Moonen, J. C.S. Kleinjans, B. van Ommen, J. H. M. van Delft, and R. H. Stierum Comparison of Coumarin-Induced Toxicity between Sandwich-Cultured Primary Rat Hepatocytes and Rats in Vivo: A Toxicogenomics Approach Drug Metab. Dispos., December 1, 2006; 34(12): 2083 - 2090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Nelson, V. Bhaskaran, W. R. Foster, and L. D. Lehman-McKeeman p53-Independent Induction of Rat Hepatic Mdm2 following Administration of Phenobarbital and Pregnenolone 16{alpha}-Carbonitrile Toxicol. Sci., December 1, 2006; 94(2): 272 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wintz, L. J. Yoo, A. Loguinov, Y.-Y. Wu, J. A. Steevens, R. D. Holland, R. D. Beger, E. J. Perkins, O. Hughes, and C. D. Vulpe Gene Expression Profiles in Fathead Minnow Exposed to 2,4-DNT: Correlation with Toxicity in Mammals Toxicol. Sci., November 1, 2006; 94(1): 71 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Q. Yin, M. Kim, J.-H. Kim, G. Kong, M.-O. Lee, K.-S. Kang, B.-I. Yoon, H.-L. Kim, and B.-H. Lee Hepatic Gene Expression Profiling and Lipid Homeostasis in Mice Exposed to Steatogenic Drug, Tetracycline Toxicol. Sci., November 1, 2006; 94(1): 206 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Moens, K. van der Ven, P. Van Remortel, J. Del-Favero, and W. M. De Coen Expression Profiling of Endocrine-Disrupting Compounds Using a Customized Cyprinus carpio cDNA Microarray Toxicol. Sci., October 1, 2006; 93(2): 298 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Powell, O. Kosyk, P. K. Ross, R. Schoonhoven, G. Boysen, J. A. Swenberg, A. N. Heinloth, G. A. Boorman, M. L. Cunningham, R. S. Paules, et al. Phenotypic Anchoring of Acetaminophen-Induced Oxidative Stress with Gene Expression Profiles in Rat Liver Toxicol. Sci., September 1, 2006; 93(1): 213 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yu, W. C. Griffith, K. Hanspers, J. F. Dillman III, H. Ong, M. A. Vredevoogd, and E. M. Faustman A System-Based Approach to Interpret Dose- and Time-Dependent Microarray Data: Quantitative Integration of Gene Ontology Analysis for Risk Assessment Toxicol. Sci., August 1, 2006; 92(2): 560 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Kim, D. J. Dix, K. E. Thompson, R. N. Murrell, J. E. Schmid, J. E. Gallagher, and J. C. Rockett Gene expression in head hair follicles plucked from men and women. Ann. Clin. Lab. Sci., March 1, 2006; 36(2): 115 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tugendreich, C. I. Pearson, J. Sagartz, K. Jarnagin, and K. Kolaja NSAID-Induced Acute Phase Response is Due to Increased Intestinal Permeability and Characterized by Early and Consistent Alterations in Hepatic Gene Expression Toxicol Pathol, February 1, 2006; 34(2): 168 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Boverhof and T. R. Zacharewski Toxicogenomics in Risk Assessment: Applications and Needs Toxicol. Sci., February 1, 2006; 89(2): 352 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. F. Cariello, E. H. Romach, H. M. Colton, H. Ni, L. Yoon, J. G. Falls, W. Casey, D. Creech, S. P. Anderson, G. R. Benavides, et al. Gene Expression Profiling of the PPAR-alpha Agonist Ciprofibrate in the Cynomolgus Monkey Liver Toxicol. Sci., November 1, 2005; 88(1): 250 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Fielden, B. P. Eynon, G. Natsoulis, K. Jarnagin, D. Banas, and K. L. Kolaja A Gene Expression Signature that Predicts the Future Onset of Drug-Induced Renal Tubular Toxicity Toxicol Pathol, October 1, 2005; 33(6): 675 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Currie, V. Bombail, J. D. Oliver, D. J. Moore, F. L. Lim, V. Gwilliam, I. Kimber, K. Chipman, J. G. Moggs, and G. Orphanides Gene Ontology Mapping as an Unbiased Method for Identifying Molecular Pathways and Processes Affected by Toxicant Exposure: Application to Acute Effects Caused by the Rodent Non-Genotoxic Carcinogen Diethylhexylphthalate Toxicol. Sci., August 1, 2005; 86(2): 453 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shostak The Emergence of Toxicogenomics: A Case Study of Molecularization Social Studies of Science, June 1, 2005; 35(3): 367 - 403. [Abstract] [PDF]
|
|
|
|
|
|
S. D. Hester, W. T. Barry, F. Zou, and D. C. Wolf Transcriptomic Analysis of F344 Rat Nasal Epithelium Suggests That the Lack of Carcinogenic Response to Glutaraldehyde is Due to its Greater Toxicity Compared to Formaldehyde Toxicol Pathol, June 1, 2005; 33(4): 415 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. M. Heijne, R.-J. A. N. Lamers, P. J. van Bladeren, J. P. Groten, J. H. J. van Nesselrooij, and B. van Ommen Profiles of Metabolites and Gene Expression in Rats with Chemically Induced Hepatic Necrosis Toxicol Pathol, June 1, 2005; 33(4): 425 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Thukral, P. J. Nordone, R. Hu, L. Sullivan, E. Galambos, V. D. Fitzpatrick, L. Healy, M. B. Bass, M. E. Cosenza, and C. A. Afshari Prediction of Nephrotoxicant Action and Identification of Candidate Toxicity-Related Biomarkers Toxicol Pathol, April 1, 2005; 33(3): 343 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Hayes, A. L. Vollrath, G. M. Zastrow, B. J. McMillan, M. Craven, S. Jovanovich, D. R. Rank, S. Penn, J. A. Walisser, J. K. Reddy, et al. EDGE: A Centralized Resource for the Comparison, Analysis, and Distribution of Toxicogenomic Information Mol. Pharmacol., April 1, 2005; 67(4): 1360 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tian, L. Cao, Y. Tan, S. Williams, L. Chen, T. Matray, A. Chenna, S. Moore, V. Hernandez, V. Xiao, et al. Multiplex mRNA assay using electrophoretic tags for high-throughput gene expression analysis Nucleic Acids Res., September 8, 2004; 32(16): e126 - e126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Gray, P. Nettesheim, C. Loftin, J.-S. Koo, J. Bonner, S. Peddada, and R. Langenbach Interleukin-1{beta}-Induced Mucin Production in Human Airway Epithelium Is Mediated by Cyclooxygenase-2, Prostaglandin E2 Receptors, and Cyclic AMP-Protein Kinase A Signaling Mol. Pharmacol., August 1, 2004; 66(2): 337 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Shultz, L. Zhang, Y.-Z. Gu, G. L. Baker, M. V. Fannuchi, A. M. Padua, W. A. Gurske, D. Morin, S. G. Penn, S. B. Jovanovich, et al. Gene Expression Analysis in Response to Lung Toxicants: I. Sequencing and Microarray Development Am. J. Respir. Cell Mol. Biol., March 1, 2004; 30(3): 296 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Naciff and G. P. Daston Toxicogenomic Approach to Endocrine Disrupters: Identification of a Transcript Profile Characteristic of Chemicals with Estrogenic Activity Toxicol Pathol, February 1, 2004; 32(2_suppl): 59 - 70. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Gray, R. Coakley, A. Hirsh, D. Thornton, S. Kirkham, J.-S. Koo, L. Burch, R. Boucher, and P. Nettesheim Regulation of MUC5AC mucin secretion and airway surface liquid metabolism by IL-1{beta} in human bronchial epithelia Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L320 - L330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ellinger-Ziegelbauer, B. Stuart, B. Wahle, W. Bomann, and H.-J. Ahr Characteristic Expression Profiles Induced by Genotoxic Carcinogens in Rat Liver Toxicol. Sci., January 1, 2004; 77(1): 19 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Michel, C. Desdouets, B. Sacre-Salem, J.-C. Gautier, R. Roberts, and E. Boitier Liver Gene Expression Profiles of Rats Treated with Clofibric Acid: Comparison of Whole Liver and Laser Capture Microdissected Liver Am. J. Pathol., December 1, 2003; 163(6): 2191 - 2199. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. RHEN, S. GRISSOM, C. AFSHARI, and J. A. CIDLOWSKI Dexamethasone blocks the rapid biological effects of 17{beta}-estradiol in the rat uterus without antagonizing its global genomic actions FASEB J, October 1, 2003; 17(13): 1849 - 1870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. MacGregor The Future of Regulatory Toxicology: Impact of the Biotechnology Revolution Toxicol. Sci., October 1, 2003; 75(2): 236 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. de Longueville, F. A. Atienzar, L. Marcq, S. Dufrane, S. Evrard, L. Wouters, F. Leroux, V. Bertholet, B. Gerin, R. Whomsley, et al. Use of a Low-Density Microarray for Studying Gene Expression Patterns Induced by Hepatotoxicants on Primary Cultures of Rat Hepatocytes Toxicol. Sci., October 1, 2003; 75(2): 378 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Gunther, D. J. Stone, R. W. Gerwien, P. Bento, and M. P. Heyes Prediction of clinical drug efficacy by classification of drug-induced genomic expression profiles in vitro PNAS, August 5, 2003; 100(16): 9608 - 9613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Guerreiro, F. Staedtler, O. Grenet, J. Kehren, and S.-D. Chibout Toxicogenomics in Drug Development Toxicol Pathol, August 1, 2003; 31(5): 471 - 479. [Abstract] [PDF]
|
|
|
|
|
|
M. L. Cunningham, M. S. Bogdanffy, T. R. Zacharewski, and R. N. Hines Workshop Overview: Use of Genomic Data in Risk Assessment Toxicol. Sci., June 1, 2003; 73(2): 209 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Lash, R. N. Hines, F. J. Gonzalez, T. R. Zacharewski, and M. A. Rothstein Genetics and Susceptibility to Toxic Chemicals: Do You (or Should You) Know Your Genetic Profile? J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 403 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Iida, C. H. Anna, J. Hartis, M. Bruno, B. Wetmore, J. R. Dubin, S. Sieber, L. Bennett, M. L. Cunningham, R. S. Paules, et al. Changes in global gene and protein expression during early mouse liver carcinogenesis induced by non-genotoxic model carcinogens oxazepam and Wyeth-14,643 Carcinogenesis, April 1, 2003; 24(4): 757 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Hamadeh, P. R. Bushel, S. Jayadev, O. DiSorbo, L. Bennett, L. Li, R. Tennant, R. Stoll, J. C. Barrett, R. S. Paules, et al. Prediction of Compound Signature Using High Density Gene Expression Profiling Toxicol. Sci., June 1, 2002; 67(2): 232 - 240. [Abstract] [Full Text] [PDF]
|
|