ArticleEnvironmental health perspectives2007
Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue.
Article in Environmental health perspectives, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 27 citations in OpenAlex.
- Robust hierarchical co-clustering for exploring toxicogenomic biomarkers and their chemical regulators.Scientific reports · 2025Article
- Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells.Toxicology · 2017Article
- Connexin-based signaling and drug-induced hepatotoxicity.Journal of clinical and translational research · 2017Article
- Sertraline induces endoplasmic reticulum stress in hepatic cells.Toxicology · 2014Article
- In vitro to in vivo extrapolation and species response comparisons for drug-induced liver injury (DILI) using DILIsym™: a mechanistic, mathematical model of DILI.Journal of pharmacokinetics and pharmacodynamics · 2012Article
- The contribution of endoplasmic reticulum stress to liver diseases.Hepatology (Baltimore, Md.) · 2011Article
- Use of transcriptomics in understanding mechanisms of drug-induced toxicity.Pharmacogenomics · 2010Review
- Discernment of possible mechanisms of hepatotoxicity via biological processes over-represented by co-expressed genes.BMC genomics · 2009Article
- Toxicogenomic biomarkers for liver toxicity.Journal of toxicologic pathology · 2009Article
- Dissection of endoplasmic reticulum stress signaling in alcoholic and non-alcoholic liver injury.Journal of gastroenterology and hepatology · 2008Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundToxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest.
objectivesThe objective of this study was to compare gene expression changes in a nontarget tissue to the target tissue for toxicity to help identify toxicity-related genes.
methodsMale rats were given the hepatotoxicant methapyrilene at two dose levels, with livers and kidneys removed 24 hr after one, three, and seven doses for gene expression analysis. To identify gene changes likely to be related to toxicity, we analyzed genes on the basis of their temporal pattern of change using a program developed at the National Institute of Environmental Health Sciences, termed "EPIG" (extracting gene expression patterns and identifying co-expressed genes).
resultsHigh-dose methapyrilene elicited hepatic damage that increased in severity with the number of doses, whereas no treatment-related lesions were observed in the kidney. High-dose methapyrilene elicited thousands of gene changes in the liver at each time point, whereas many fewer gene changes were observed in the kidney. EPIG analysis identified patterns of gene expression correlated to the observed toxicity, including genes associated with endoplasmic reticulum stress and the unfolded protein response.
conclusionsBy factoring in dose level, number of doses, and tissue into the analysis of gene expression elicited by methapyrilene, we were able to identify genes likely to not be implicated in toxicity, thereby allowing us to focus on a subset of genes to identify toxicity-related processes.
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