Transcriptional effects of PFOS in isolated hepatocytes from Atlantic salmon Salmo salar L

Comp Biochem Physiol C Toxicol Pharmacol. 2008 Jul;148(1):14-22. doi: 10.1016/j.cbpc.2008.03.001. Epub 2008 Mar 12.

Abstract

The main aim of the current in vitro experiment was to search for makers for PFOS exposure in isolated hepatocytes from Atlantic salmon Salmo salar, based on genes responding to PFOS exposure in other animals. Primary cell cultures of hepatocytes were exposed to four concentrations of PFOS (2.1-6.2-15.1-25.0 mg/L) for 24 and 48 h and the transcriptional levels of 12 genes encoding proteins known to respond to PFOS were quantified with real-time RT-PCR. The 12 examined genes were caspase 3B (apoptosis), GSH-Px and HSP70 (cellular stress), CYP1A, CYP3A, GST and UGT (P450 and phase II enzymes), acyl-CoA oxidase, PPARalpha, PPARbeta and PPARgamma (lipid metabolism) and Na(+)-K(+)-ATPase (ion regulation). Most of the studied genes responded in a dose-dependent manner to PFOS exposure, although the transcriptional differences in general where small with regard to fold change. Our results clearly suggest that PFOS exposure enhanced cellular stress in the examined cells, even though the exact mechanisms behind this stress remain unknown. The results from this in vitro experiment showed that genes known to be affected by PFOS exposure in other species also were induced in hepatocytes of Atlantic salmon, giving us the rationale to expand to testing the actual in vivo magnitude of effect in Atlantic salmon exposed to PFOS at doses usually seen in nature/diets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonic Acids / toxicity*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biomarkers / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Dose-Response Relationship, Drug
  • Environmental Monitoring / methods
  • Fish Proteins / genetics
  • Fish Proteins / metabolism*
  • Fluorocarbons / toxicity*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hepatocytes / drug effects*
  • Hepatocytes / enzymology
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Metabolic Detoxication, Phase II / genetics
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salmo salar / genetics
  • Salmo salar / metabolism*
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Time Factors
  • Transcription, Genetic / drug effects*
  • Water Pollutants, Chemical / toxicity*

Substances

  • Alkanesulfonic Acids
  • Biomarkers
  • Fish Proteins
  • Fluorocarbons
  • Water Pollutants, Chemical
  • Cytochrome P-450 Enzyme System
  • perfluorooctane sulfonic acid
  • Sodium-Potassium-Exchanging ATPase