Title
Toxicogenomic analysis of gene expression changes in rat liver after a 28-day oral benzene exposure
Author
Heijne, W.H.M.
Jonker, D.
Stierum, R.H.
van Ommen, B.
Groten, J.P.
TNO Kwaliteit van Leven
Publication year
2005
Abstract
Benzene is an industrial chemical, component of automobile exhaust and cigarette smoke. After hepatic bioactivation benzene induces bone marrow, blood and hepatic toxicity. Using a toxicogenomics approach this study analysed the effects of benzene at three dose levels on gene expression in the liver after 28 daily doses. NMR based metabolomics was used to assess benzene exposure by identification of characteristic benzene metabolite profiles in urine. The 28-day oral exposure to 200 and 800 mg/kg/day but not 10 mg/kg/day benzene-induced hematotoxicity in male Fisher rats. Additionally these upper dose levels slightly reduced body weight and increased relative liver weights. Changes in hepatic gene expression were identified with oligonucleotide microarrays at all dose levels including the 10 mg/kg/day dose level where no toxicity was detected by other methods. The benzene-induced gene expression changes were related to pathways of biotransformation, glutathione synthesis, fatty acid and cholesterol metabolism and others. Some of the effects on gene expression observed here have previously been observed after induction of acute hepatic necrosis with bromobenzene and acetaminophen. In conclusion, changes in hepatic gene expression were found after treatment with benzene both at the toxic and non-toxic doses. The results from this study show that toxicogenomics identified hepatic effects of benzene exposure possibly related to toxicity. The findings aid to interpret the relevance of hepatic gene expression changes in response to exposure to xenobiotics. In addition, the results have the potential to inform on the mechanisms of response to benzene exposure. © 2005 Elsevier B.V. All rights reserved.
Subject
Toxicology Biology
Toxicology and Applied Pharmacology
Benzene
cDNA microarrays
Gene expression
Hepatotoxicity
Metabolomics
Toxicogenomics
Transcriptomics
benzene
bromobenzene
paracetamol
animal experiment
animal tissue
biotransformation
blood toxicity
cholesterol metabolism
conference paper
DNA microarray
gene expression
genetic analysis
genetic toxicology
glutathione metabolism
liver necrosis
liver weight
male
nonhuman
nuclear magnetic resonance spectroscopy
nucleotide sequence
priority journal
rat
rat strain
unindexed sequence
Animals
Benzene
Blood Cell Count
Cholesterol
Fatty Acids
Gene Expression Profiling
Gene Expression Regulation
Hemoglobins
Liver
Male
Mutagens
Oligonucleotide Array Sequence Analysis
Organ Size
Rats
Rats, Inbred F344
Spleen
Thymus Gland
Time Factors
Urinalysis
Martes pennanti
To reference this document use:
http://resolver.tudelft.nl/uuid:f617cda9-abd3-4843-b775-4c7f3df757cf
DOI
https://doi.org/10.1016/j.mrfmmm.2005.02.003
TNO identifier
238643
ISSN
0027-5107
Source
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 575 (1-2), 85-101
Document type
article