Altered expression of hepatic metabolic enzyme and apoptosis-related gene transcripts in human hepatocytes treated with trichloroethylene

Hum Exp Toxicol. 2012 Sep;31(9):861-7. doi: 10.1177/0960327112444935. Epub 2012 Jun 29.

Abstract

Trichloroethylene (TCE) is a common organic solvent that has been widely used in industrial applications. Hundred cases of allergic reactions occurred after the workers were occupationally exposed to TCE in China in the past decade, but the underlying effector mechanisms of TCE remain unclear. The purpose of the present study is to examine the alteration of hepatic metabolic enzyme gene and apoptosis-related gene messenger RNA (mRNA) expression in L02 human hepatocytes (L02 cells) after treatment with TCE. L02 cells were cultured either with various doses of TCE (0.25, 0.5, 1.0 and 2.0 mmol/L) for 24 h or with a single dose of TCE (1.0 mmol/L) for different time intervals, whereas samples treated with dimethyl sulfoxide served as control. Quantitative real-time polymerase chain reaction analysis was performed to detect the mRNA expression of hepatic metabolic enzyme genes (CYP1A2, CYP3A4 and CYP2E1) and apoptosis-related genes (BAX and BAD). It was found that the transcript levels of hepatic metabolic enzyme genes and apoptosis genes including BAX and BAD were significantly increased after TCE treatment at various doses for 24 h when compared with controls. Additionally, when the cells were treated with a single dose of TCE (1.0 mmol/L) for different periods of time (3, 6, 12 and 24 h), the mRNA expression of these genes also increased significantly compared with control (p < 0.05 or p < 0.01). The conclusion of the study is that TCE could induce alteration of mRNA expression of hepatic metabolic enzyme genes and apoptosis genes, which might be implicated in the effector mechanisms of TCE cytotoxicity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line
  • Cell Survival / drug effects
  • Cytochrome P-450 CYP1A2 / genetics
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP3A / genetics
  • Gene Expression Regulation / drug effects*
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Liver / metabolism
  • RNA, Messenger / metabolism
  • Solvents / toxicity*
  • Trichloroethylene / toxicity*
  • bcl-2-Associated X Protein / genetics
  • bcl-Associated Death Protein / genetics

Substances

  • BAD protein, human
  • BAX protein, human
  • RNA, Messenger
  • Solvents
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • Trichloroethylene
  • Cytochrome P-450 CYP2E1
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human