US EPA

4973148 

Journal Article 

Copper Ions Differ from Other Thiol Reactive Metal Ions in Their Effects on the Concentration and Redox Status of Thiols in HeLa Cell Cultures 

Hultberg, B; Andersson, A; Isaksson, A 

1997 

1 

Toxicology
ISSN: 0300-483X
EISSN: 1879-3185 

117 

In an effort to determine the cytotoxic effects of copper (7440508) ions in comparison with some other thiol reactive metal ions including mercury (7439976), silver (7440224), and cadmium (7440439), a study was done to measure cell growth and concentrations and redox status of glutathione, cysteine, and homocysteine in a cell culture system following the addition of metal ions. When HeLa cells in culture were treated with 0.1 micromole/liter of each of the metal ions, no effect was seen on the total intracellular thiol concentrations or amounts excreted to the medium. When cells were treated with metal ions, at concentrations which did not affect the growth of the cells, an increase in the release of glutathione into the medium was seen. Since the intracellular level of glutathione did not decrease under these conditions, the synthesis of glutathione must have therefore been increased. The reason for the increased glutathione release into the medium was not clear. Although it was observed that an increased concentration of reduced extracellular glutathione occurred after the addition of mercury, silver and cadmium ions, the ratios between the reduced and total concentrations of extracellular glutathione were decreased to about 30% compared to 50% found in normal conditions. Following addition of copper ions, the concentration of extracellular reduced glutathione was decreased in spite of the increased amount of total extracellular glutathione. In contrast to the other metal ions, the addition of even very low concentrations of copper ions seemed to increase the oxidative stress in the cells, indicated by a decrease in the concentration of intracellular and extracellular reduced thiols. Copper ions also increased release of homocysteine into the medium, perhaps through an interaction with S-adenosylhomocysteine-hydrolase in contrast to the other metal ions.