Bromobenzene-induced hepatotoxicity at the transcriptome level
| Autor: | Ben van Ommen, Wilbert H.M. Heijne, Angela L. Slitt, Rob H. Stierum, Curtis D. Klaassen, John P. Groten, T. Peter J. Van Bladeren |
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| Přispěvatelé: | TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
Time Factors binding Transcription Genetic Acute phase response Signal transduction Protein depletion Toxicology Animal tissue Transcriptome Gene expression Biology Toxicology glutathione induction Cytoskeleton Oligonucleotide Array Sequence Analysis acetaminophen Regulation of gene expression Gene rearrangement Messenger RNA glyceraldehyde-3-phosphate dehydrogenase gene element Transcription regulation Toxicogenomics Complementary DNA DNA responsive element Gene expression profiling Cholesterol Biochemistry Liver Chemical and Drug Induced Liver Injury Liver toxicity DNA determination Physiological Sciences rat-liver Biology Concentration response Cell communication Electron Cytochrome P450 4A Protein metabolism expression Cholesterol metabolism Animals Animal model Animal experiment acute-phase response Transcriptomics Toxicologie Sterol VLAG cDNA microarray Gene amplification Drug metabolism Bromobenzene Microarray analysis techniques Protein Gene Expression Profiling Hepatotoxicity DNA microarray Rats Inbred Strains Fatty acid Nonhuman Microarray Analysis Molecular biology Rats Gene Expression Regulation Oxidative stress Fatty acid metabolism Rat identification Metallothionein Hepatitis Toxic Protein synthesis Peroxiredoxin Controlled study Nucleotide sequence Bromobenzenes |
| Zdroj: | Toxicological sciences, 79(2), 411-422 Toxicological sciences 79 (2004) 2 Toxicological Sciences, 2, 79, 411-422 |
| ISSN: | 1096-6080 |
| Popis: | Rats were exposed to three levels of bromobenzene, sampled at 6, 24, and 48 h, and liver gene expression profiles were determined to identify dose and time-related changes. Expression of many genes changed transiently, and dependent on the dose. Few changes were identified after 6 h, but many genes were differentially expressed after 24 h, while after 48 h, only the high dose elicited large effects. Differentially expressed genes were involved in drug metabolism (upregulated GSTs, mEH, NQO1, Mrps, downregulated CYPs, sulfotransferases), oxidative stress (induced HO-1, peroxiredoxin, ferritin), GSH depletion (induced GCS-1, GSTA, GSTM) the acute phase response, and in processes like cholesterol, fatty acid and protein metabolism, and intracellular signaling. Trancriptional regulation via the electrophile and sterol response elements seemed to mediate part of the response to bromobenzene. Recovery of the liver was suggested in response to BB by the altered expression of genes involved in protein synthesis and cytoskeleton rearrangement. Furthermore, after 48 h, rats in the mid dose group showed no toxicity, and gene expression patterns resembled the normal situation. For certain genes (e.g., CYP4A, metallothioneins), intraday variation in expression levels was found, regardless of the treatment. Selected cDNA microarray measurements were confirmed using the specific and sensitive branched DNA signal amplification assay. © Society of Toxicology 2004; all rights reserved. |
| Databáze: | OpenAIRE |
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