ArticleEnvironmental health perspectives2004
Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene.
Article in Environmental health perspectives, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 71 citations in OpenAlex.
- Connexin-based signaling and drug-induced hepatotoxicity.Journal of clinical and translational research · 2017Article
- A metabolomics investigation of non-genotoxic carcinogenicity in the rat.Journal of proteome research · 2013Article
- Practical application of toxicogenomics for profiling toxicant-induced biological perturbations.International journal of molecular sciences · 2010Review
- Use of transcriptomics in understanding mechanisms of drug-induced toxicity.Pharmacogenomics · 2010Review
- Toxicogenomic biomarkers for liver toxicity.Journal of toxicologic pathology · 2009Article
- Systems biology and functional genomics approaches for the identification of cellular responses to drug toxicity.Expert opinion on drug metabolism & toxicology · 2008Review
- Randomization in laboratory procedure is key to obtaining reproducible microarray results.PloS one · 2008Article
- Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue.Environmental health perspectives · 2007Article
- Gene expression analysis of the hepatotoxicant methapyrilene in primary rat hepatocytes: an interlaboratory study.Environmental health perspectives · 2006Article
- Optimal sampling of rat liver tissue for toxicogenomic studies.Toxicologic pathology · 2006Article
- Recent applications of DNA microarray technology to toxicology and ecotoxicology.Environmental health perspectives · 2006Review
- Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression.Environmental health perspectives · 2004Article
- Quantitative PCR deconstruction of discrepancies between results reported by different hybridization platforms.Environmental health perspectives · 2004Article
- Toxicogenomics in risk assessment: an overview of an HESI collaborative research program.Environmental health perspectives · 2004Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several studies using microarrays have shown that changes in gene expression provide information about the mechanism of toxicity induced by xenobiotic agents. Nevertheless, the issue of whether gene expression profiles are reproducible across different laboratories remains to be determined. To address this question, several members of the Hepatotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute evaluated the liver gene expression profiles of rats treated with methapyrilene (MP). Animals were treated at one facility, and RNA was distributed to five different sites for gene expression analysis. A preliminary evaluation of the number of modulated genes uncovered striking differences between the five different sites. However, additional data analysis demonstrated that these differences had an effect on the absolute gene expression results but not on the outcome of the study. For all users, unsupervised algorithms showed that gene expression allows the distinction of the high dose of MP from controls and low dose. In addition, the use of a supervised analysis method (support vector machines) made it possible to correctly classify samples. In conclusion, the results show that, despite some variability, robust gene expression changes were consistent between sites. In addition, key expression changes related to the mechanism of MP-induced hepatotoxicity were identified. These results provide critical information regarding the consistency of microarray results across different laboratories and shed light on the strengths and limitations of expression profiling in drug safety analysis.
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Registered trials
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