Comparative study on methyl- and ethylmercury-induced toxicity in C6 glioma cells and the potential role of LAT-1 in mediating mercurial-thiol complexes uptake

Neurotoxicology. 2013 Sep;38:1-8. doi: 10.1016/j.neuro.2013.05.015. Epub 2013 May 30.


Various forms of mercury possess different rates of absorption, metabolism and excretion, and consequently, toxicity. Methylmercury (MeHg) is a highly neurotoxic organic mercurial. Human exposure is mostly due to ingestion of contaminated fish. Ethylmercury (EtHg), another organic mercury compound, has received significant toxicological attention due to its presence in thimerosal-containing vaccines. This study was designed to compare the toxicities induced by MeHg and EtHg, as well as by their complexes with cysteine (MeHg-S-Cys and EtHg-S-Cys) in the C6 rat glioma cell line. MeHg and EtHg caused significant (p<0.0001) decreases in cellular viability when cells were treated during 30min with each mercurial following by a washing period of 24h (EC50 values of 4.83 and 5.05μM, respectively). Significant cytotoxicity (p<0.0001) was also observed when cells were treated under the same conditions with MeHg-S-Cys and EtHg-S-Cys, but the respective EC50 values were significantly increased (11.2 and 9.37μM). l-Methionine, a substrate for the l-type neutral amino acid carrier transport (LAT) system, significantly protected against the toxicities induced by both complexes (MeHg-S-Cys and EtHg-S-Cys). However, no protective effects of l-methionine were observed against MeHg and EtHg toxicities. Corroborating these findings, l-methionine significantly decreased mercurial uptake when cells were exposed to MeHg-S-Cys (p=0.028) and EtHg-S-Cys (p=0.023), but not to MeHg and EtHg. These results indicate that the uptake of MeHg-S-Cys and EtHg-S-Cys into C6 cells is mediated, at least in part, through the LAT system, but MeHg and EtHg enter C6 cells by mechanisms other than LAT system.

Keywords: Ethylmercury; Methylmercury; Toxicity; l-Type neutral amino acid carrier transport.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System L / metabolism*
  • Animals
  • Biological Transport / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / antagonists & inhibitors
  • Coordination Complexes / chemistry
  • Coordination Complexes / metabolism
  • Coordination Complexes / toxicity
  • Cysteine / chemistry
  • Cysteine / toxicity*
  • Ethylmercuric Chloride / antagonists & inhibitors
  • Ethylmercuric Chloride / chemistry
  • Ethylmercuric Chloride / metabolism*
  • Ethylmercuric Chloride / toxicity*
  • Glioma / metabolism
  • Glioma / pathology*
  • Glutathione / drug effects
  • Glutathione / metabolism
  • Hippocampus / metabolism
  • Methionine / pharmacology
  • Methylmercury Compounds / antagonists & inhibitors
  • Methylmercury Compounds / chemistry
  • Methylmercury Compounds / metabolism*
  • Methylmercury Compounds / toxicity*
  • Rats


  • Amino Acid Transport System L
  • Coordination Complexes
  • Methylmercury Compounds
  • Methionine
  • Glutathione
  • Cysteine
  • Ethylmercuric Chloride
  • methylmercuric chloride