Changes in gene expression induced by polycyclic aromatic hydrocarbons in the human cell lines HepG2 and A549

Toxicol In Vitro. 2008 Mar;22(2):411-21. doi: 10.1016/j.tiv.2007.10.009.

Abstract

Polycyclic aromatic hydrocarbons (PAH) are the main components of emissions generated by coke oven factories and many of these chemicals are carcinogenic. The goal of this study was to examine changes in gene expression in two human cell lines, HepG2 and A549, induced by exposure to a soil extract containing PAH using microarry technology. Soil samples were obtained from the vicinity of a coke oven factory in northeastern Mexico. For comparison, the gene expression pattern induced by Benz[a]pyrene (BaP) was also analyzed. The number of altered genes by both treatments was 2-fold higher in hepatic than in pulmonary cells. Differentially-modulated genes in the two cell lines were identified and grouped by biological function using genomic databases. A group of nine genes up- and down-regulated by either the PAH extract or BaP were selected for validation by real-time PCR. The cellular functions of these PAH-responsive genes included: xenobiotic metabolism (CYP1A1 and CYP1B1), DNA repair (ERCC5), oxidative stress response and cell proliferation (FTH1 and PRDX1), protein degradation (PSMD7), ion transport (FXYD3), steroid biosynthesis (FDFT1), and signaling pathways (PTGER3). The real-time PCR analysis confirmed most of the microarray data with significant correlation. Additional studies are required to determine the mechanisms involved in the PAH-mediated modulation of these genes and to associate these changes with human health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogens / toxicity*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coke / analysis
  • Data Collection
  • Environmental Pollutants / toxicity*
  • Gene Expression / drug effects*
  • Gene Expression Profiling
  • Humans
  • In Situ Hybridization
  • Indicators and Reagents
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Polycyclic Aromatic Hydrocarbons / toxicity*
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Soil Pollutants / chemistry
  • Soil Pollutants / toxicity
  • Xenobiotics / metabolism

Substances

  • Carcinogens
  • Coke
  • Environmental Pollutants
  • Indicators and Reagents
  • Polycyclic Aromatic Hydrocarbons
  • RNA, Neoplasm
  • Soil Pollutants
  • Xenobiotics