Toxicogenomics of bromobenzene hepatotoxicity: a combined transcriptomics and proteomics approach

摘要: Toxicogenomics is a novel approach integrating the expression analysis of thousands genes (transcriptomics) or proteins (proteomics) with classical methods in toxicology. Effects at molecular level are related to pathophysiological changes organisms, enabling detailed comparison mechanisms and early detection prediction toxicity. This report addresses value combined use transcriptomics proteomics technologies Acute hepatotoxicity was induced rats by bromobenzene administration resulting depleted glutathione levels reduced average body weights, 24hr after dosage. These physiological symptoms coincided many hepatic mRNA protein content. Gene induction confirmed involvement glutathione-S-transferase isozymes epoxide hydrolase metabolism identified possibly relevant Observed depletion key enzyme biosynthesis, γ-glutamylcysteine synthetase. Oxidative stress apparent from strong upregulation heme oxygenase, peroxiredoxin 1 other genes. Bromobenzene-induced degradation suggested two-dimensional gel electrophoresis, upregulated for proteasome subunits lysosomal cathepsin L, whereas also were role synthesis. Both gene profiles treated clearly distinct controls as shown principal component analysis, several found significantly change upon treatment mass spectrometry. A modest overlap results found. work indicates that complementary each provide new possibilities © 2002 Elsevier Science Inc. All rights reserved.