ArticleArchives of toxicology2018
Toxicogenomics directory of rat hepatotoxicants in vivo and in cultivated hepatocytes.
Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens.International journal of molecular sciences · 2022Review
- RAID: Regression Analysis-Based Inductive DNA Microarray for Precise Read-Across.Frontiers in pharmacology · 2022Article
- Enigmatic mechanism of the N-vinylpyrrolidone hepatocarcinogenicity in the rat.Archives of toxicology · 2021Article
- Roadmap for the development of alternative test methods.Archives of toxicology · 2020Article
- Role of autophagy in drug induced liver injury.Archives of toxicology · 2020Article
- Hepatotoxicity of pyrrolizidine alkaloids in rats in relation to human exposure.Archives of toxicology · 2020Article
- Hepatotoxic pyrrolizidine alkaloids induce DNA damage response in rat liver in a 28-day feeding study.Archives of toxicology · 2020Article
- Do artificial sweeteners increase the risk of non-alcoholic fatty liver disease (NAFLD)?EXCLI journal · 2020Article
- RNA-protein correlation of liver toxicity markers in HepaRG cells.EXCLI journal · 2020Article
- PPARG as therapeutic target for antifibrotic therapy.EXCLI journal · 2020Article
- Highlight Report: Hepatobiliary differentiation from human induced pluripotent stem cells.EXCLI journal · 2020Article
- Hepatotoxicity of anesthetic gases.EXCLI journal · 2020Article
- Which concentrations are optimal forEXCLI journal · 2020Article
- Letter to the editor.Archives of toxicology · 2019Article
- Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations.Archives of toxicology · 2019Article
- Narrowing the Gap BetweenFrontiers in pharmacology · 2019Article
- Highlight report: Toxicogenomics atlas of rat hepatotoxicants.EXCLI journal · 2018Article
- Highlight report: Necrosis-apoptosis conundrum of hepatocytes: mode of hepatocyte death after acetaminophen intoxication.EXCLI journal · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
23 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptomics is developing into an invaluable tool in toxicology. The aim of this study was, using a transcriptomics approach, to identify genes that respond similar to many different chemicals (including drugs and industrial compounds) in both rat liver in vivo and in cultivated hepatocytes. For this purpose, we analyzed Affymetrix microarray expression data from 162 compounds that were previously tested in a concentration-dependent manner in rat livers in vivo and in rat hepatocytes cultivated in sandwich culture. These data were obtained from the Japanese Toxicogenomics Project (TGP) and North Rhine-Westphalian (NRW) data sets, which represent 138 and 29 compounds, respectively, and have only 5 compounds in common between them. The in vitro gene expression data from the NRW data set were generated in the present study, while TGP is publicly available. For each of the data sets, the overlap between up- or down-regulated genes in vitro and in vivo was identified, and named in vitro-in vivo consensus genes. Interestingly, the in vivo-in vitro consensus genes overlapped to a remarkable extent between both data sets, and were 21-times (upregulated genes) or 12-times (down-regulated genes) enriched compared to random expectation. Finally, the genes in the TGP and NRW overlap were used to identify the upregulated genes with the highest compound coverage, resulting in a seven-gene set of Cyp1a1, Ugt2b1, Cdkn1a, Mdm2, Aldh1a1, Cyp4a3, and Ehhadh. This seven-gene set was then successfully tested with structural analogues of valproic acid that are not present in the TGP and NRW data sets. In conclusion, the seven-gene set identified in the present study responds similarly in vitro and in vivo to a wide range of different chemicals. Despite these promising results with the seven-gene set, transcriptomics with cultivated rat hepatocytes remains a challenge, because in general many genes are up- or downregulated by in vitro culture per se, respond differently to test compounds in vitro and in vivo, and/or show higher variability in the in vitro system compared to the corresponding in vivo data.
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