Trichloroethylene-induced gene expression and DNA methylation changes in B6C3F1 mouse liver

PLoS One. 2014 Dec 30;9(12):e116179. doi: 10.1371/journal.pone.0116179. eCollection 2014.

Abstract

Trichloroethylene (TCE), widely used as an organic solvent in the industry, is a common contaminant in air, soil, and water. Chronic TCE exposure induced hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s) for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE (0, 100, 500 and 1000 mg/kg b.w. per day) for 5 days. After 5 days TCE treatment at a dose level of 1000 mg/kg b.w., a total of 431 differentially expressed genes were identified in mouse liver by microarray, of which 291 were up-regulated and 140 down-regulated. The expression changed genes were involved in key signal pathways including PPAR, proliferation, apoptosis and homologous recombination. Notably, the expression level of a number of vital genes involved in the regulation of DNA methylation, such as Utrf1, Tet2, DNMT1, DNMT3a and DNMT3b, were dysregulated. Although global DNA methylation change was not detected in the liver of mice exposed to TCE, the promoter regions of Cdkn1a and Ihh were found to be hypo- and hypermethylated respectively, which correlated negatively with their mRNA expression changes. Furthermore, the gene expression and DNA methylation changes induced by TCE were dose dependent. The overall data indicate that TCE exposure leads to aberrant DNA methylation changes, which might alter the expression of genes involved in the TCE-induced liver tumorgenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cells, Cultured
  • DNA Methylation / drug effects*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Liver / drug effects*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic / drug effects
  • Signal Transduction / drug effects
  • Trichloroethylene / administration & dosage*
  • Trichloroethylene / pharmacology

Substances

  • Trichloroethylene

Associated data

  • GEO/GSE58819

Grant support

This work was supported by the start-up funding of Soochow University and The Priority Academic Program Development of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.