Ions of metals such as
mercury,
cadmium and
copper are known to exhibit a high affinity for
thiol groups and may therefore severely disturb many metabolic functions in the cell. The aim of the present study was to identify the most sensitive changes of
thiol metabolism induced by the addition of low concentrations of
metal ions in order to elucidate the mechanisms of
metal-toxicity. The effects on
thiol metabolism by
copper ions seemed to differ from that of
mercury and
cadmium ions.
Copper ions exhibited mainly two effects that were different from those of
mercury and
cadmium ions. They lowered the reduced fractions of
thiols and increased the release of
homocysteine into the medium, whereas
mercury and
cadmium ions mainly influenced the metabolism of
glutathione by increasing its synthesis. Even 0.1 micromol/l of
copper ions increased the release of
homocysteine in HeLa cell lines. An increased cellular concentration of
glutathione and an increased release of
glutathione into the medium were observed after addition of
mercury and
cadmium ions at a concentration of 1 micromol/l, which is just above the toxicity limit in human blood. The different cell lines varied in some respects in their response to the addition of
metal ions.
Cadmium ions had no effect on
thiol metabolism in endothelial cell lines, and
copper ions did not significantly increase the release of
homocysteine into the medium in
hepatoma cell lines. Furthermore, the metabolism of
thiols during basal conditions (without the addition of
metal ions) differed somewhat in the three cell lines investigated. One example is the low amount of extracellular
glutathione in
hepatoma cell lines, which probably was due to its rapid degradation to
cysteinylglycine by
gamma-glutamyl-transpeptidase.