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University of North Carolina-Chapel Hill: Dataset Details, ID=GSE100296

Superfund Research Program

Elucidating Risks: From Exposure and Mechanism to Outcome

Center Director: Rebecca C. Fry
Grant Number: P42ES005948
Funding Period: 1992-2018
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Title: Comparative dose-response analysis of liver and kidney transcriptomic effects of trichloroethylene and tetrachloroethylene in B6C3F1 mouse

Accession Number: GSE100296

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100296

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Array expression profiling by high throughput sequencing

Organism(s): Mus musculus

Summary: Purpose: Trichloroethylene (TCE) and tetrachloroethylene (PCE) are ubiquitous environmental contaminants and occupational health hazards. The goals of this study were to establish the common and differing transcriptional effects of TCE and PCE. This study examined liver and kidney effects of TCE and PCE in a dose-response study design. Methods: Equi-molar doses of TCE (24, 80, 240, 800 mg/kg) or PE (30, 100, 300, 1,000 mg/kg) were administered by gavage in aqueous vehicle to male B6C3F1/J mice. Tissues were collected 24 hrs after exposure. Trichloroacetic acid (TCA), a major oxidative metabolite of both compounds, was measured and RNA sequencing was performed on liver and kidney samples, with ~30 samples for each organ (29 after QC). Results: Most dose-responsive pathways were common among chemicals/tissues, with the strongest effect on peroxisomal beta-oxidation. Effects on liver and kidney mitochondria-related pathways were notably unique to PCE. Tissue-specific acute transcriptional effects of TCE and PCE occurred at human equivalent doses comparable to those for apical effects. Conclusions: Our study is the first RNA-Seq transcriptional study of TCE vs. PCE in both liver and kidney, enabling a detailed comparison of the chemicals and effects on different organs. Our results show strong commonalities of effects, although PCE shows stronger transcriptional responses than TCE for the same equimolar doses.

Publication(s) associated with this dataset:
  • Zhou Y, Cichocki JA, Soldatow VY, Scholl EH, Gallins P, Jima DD, Yoo HS, Chiu WA, Wright FA, Rusyn I. 2017. Editor's highlight: comparative dose-response analysis of liver and kidney transcriptomic effects of trichloroethylene and tetrachloroethylene in B6C3F1 mouse. Toxicol Sci 160(1):95-110. doi:10.1093/toxsci/kfx165 PMID:28973375 PMCID:PMC5837274
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