Antagonistic effects of methyl-mercury and PCB153 on PC12 cells after a combined and simultaneous exposure

Food Chem Toxicol. 2006 Sep;44(9):1505-12. doi: 10.1016/j.fct.2006.04.009. Epub 2006 Apr 26.

Abstract

The study of interactions for those substances which tend to accumulate in food and affect the nervous system appears to be a fundamental point to characterize the combined exposure in vitro. In this study we included two food contaminants which are known neurotoxicants: methyl-mercury (Me-Hg) and the ortho-substituted PCB 153. PC12 cells were treated with Me-Hg (range 1e-7, 2e-6 M) and PCB153 (range 1e-5, 4e-4 M) in single and combined synchronous experiments and a mathematical model was set up according to the Loewe additivity criterion to evaluate the level of interaction between toxicants, using viability as end-point. At some concentrations (Me-Hg 5e-7 M and PCB153 1e-4 and 2e-4 M; Me-Hg 1e-6M and PCB153 5e-5 M; Me-Hg 1e-7 M and PCB153 4e-4 M), a statistically significant antagonist effect was observed. No interaction was observed for other combinations. The analysis of other toxicological parameters known to be modified in single exposure experiments (TBARS and intra-cellular dopamine) confirmed the viability results. The results of our work represent a starting point to generate novel information on the interactions between PCB153 and Me-Hg in vitro, as well as a new relevant experimental and mathematical approach useful to investigate the effects of different toxicant mixtures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Drug Antagonism
  • Drug Combinations
  • Environmental Pollutants / toxicity
  • Food Contamination*
  • Formazans / metabolism
  • Lipid Peroxidation / drug effects
  • Methylmercury Compounds / toxicity*
  • Models, Biological
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurotoxicity Syndromes / etiology
  • PC12 Cells / drug effects*
  • PC12 Cells / metabolism
  • Polychlorinated Biphenyls / toxicity*
  • Rats
  • Tetrazolium Salts / metabolism
  • Thiobarbiturates / metabolism

Substances

  • Drug Combinations
  • Environmental Pollutants
  • Formazans
  • Methylmercury Compounds
  • Tetrazolium Salts
  • Thiobarbiturates
  • MTT formazan
  • Polychlorinated Biphenyls
  • methylmercury hydroxide
  • thiobarbituric acid
  • Dopamine