ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Editor's Highlight: Collaborative Cross Mouse Population Enables Refinements to Characterization of the Variability in Toxicokinetics of Trichloroethylene and Provides Genetic Evidence for the Role of PPAR Pathway in Its Oxidative Metabolism.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Systematic cell-type resolved transcriptomes of 8 tissues in 8 lab and wild-derived mouse strains capture global and local expression variation.Cell genomics · 2026Article
- Characterizing common loss-of-function genes and their potential utility in assessing population variability and chemical susceptibility.bioRxiv : the preprint server for biology · 2025Article
- The mouse resource at National Resource Center for Mutant Mice of China.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Structure-specific variation in per- and polyfluoroalkyl substances toxicity among genetically diverse Caenorhabditis elegans strains.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!Journal of toxicology and environmental health. Part B, Critical reviews · 2025Review
- Model systems and organisms for addressing inter- and intra-species variability in risk assessment.Regulatory toxicology and pharmacology : RTP · 2022Review
- Integrative analysis reveals mouse strain-dependent responses to acute ozone exposure associated with airway macrophage transcriptional activity.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Intra- and Inter-Species Variability in Urinary N7-(1-Hydroxy-3-buten-2-yl)guanine Adducts Following Inhalation Exposure to 1,3-Butadiene.Chemical research in toxicology · 2021Article
- Quantitative Characterization of Population-Wide Tissue- and Metabolite-Specific Variability in Perchloroethylene Toxicokinetics in Male Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Characterization of genetically complex Collaborative Cross mouse strains that model divergent locomotor activating and reinforcing properties of cocaine.Psychopharmacology · 2020Article
- Trichloroethylene, a ubiquitous environmental contaminant in the risk for Parkinson's disease.Environmental science. Processes & impacts · 2020Article
- High-Diversity Mouse Populations for Complex Traits.Trends in genetics : TIG · 2019Review
- Using Collaborative Cross Mouse Population to Fill Data Gaps in Risk Assessment: A Case Study of Population-Based Analysis of Toxicokinetics and Kidney Toxicodynamics of Tetrachloroethylene.Environmental health perspectives · 2019Article
- Population-Based Analysis of DNA Damage and Epigenetic Effects of 1,3-Butadiene in the Mouse.Chemical research in toxicology · 2019Article
- Determinants of QTL Mapping Power in the Realized Collaborative Cross.G3 (Bethesda, Md.) · 2019Article
- Whole Genome Sequencing and Progress Toward Full Inbreeding of the Mouse Collaborative Cross Population.G3 (Bethesda, Md.) · 2019Article
- The Collaborative Cross: A Systems Genetics Resource for Studying Host-Pathogen Interactions.Cell host & microbe · 2019Review
- 2018 Toxicological Sciences Papers of the Year.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains.Toxicology · 2018Article
- Perinatal nutrition interacts with genetic background to alter behavior in a parent-of-origin-dependent manner in adult Collaborative Cross mice.Genes, brain, and behavior · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Background: Trichloroethylene (TCE) is a known carcinogen in humans and rodents. Previous studies of inter-strain variability in TCE metabolism were conducted in multi-strain panels of classical inbred mice with limited genetic diversity to identify gene-environment interactions associated with chemical exposure. Objectives: To evaluate inter-strain variability in TCE metabolism and identify genetic determinants that are associated with TCE metabolism and effects using Collaborative Cross (CC), a large panel of genetically diverse strains of mice. Methods: We administered a single oral dose of 0, 24, 80, 240, or 800 mg/kg of TCE to mice from 50 CC strains, and collected organs 24 h post-dosing. Levels of trichloroacetic acid (TCA), a major oxidative metabolite of TCE were measured in multiple tissues. Protein expression and activity levels of TCE-metabolizing enzymes were evaluated in the liver. Liver transcript levels of known genes perturbed by TCE exposure were also quantified. Genetic association mapping was performed on the acquired phenotypes. Results: TCA levels varied in a dose- and strain-dependent manner in liver, kidney, and serum. The variability in TCA levels among strains did not correlate with expression or activity of a number of enzymes known to be involved in TCE oxidation. Peroxisome proliferator-activated receptor alpha (PPARα)-responsive genes were found to be associated with strain-specific differences in TCE metabolism. Conclusions: This study shows that CC mouse population is a valuable tool to quantitatively evaluate inter-individual variability in chemical metabolism and to identify genes and pathways that may underpin population differences.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.