ALTERATIONS OF THIOL METABOLISM IN HUMAN CELL-LINES INDUCED BY LOW AMOUNTS OF COPPER, MERCURY OR CADMIUM IONS

Ions of metals such as mercury, cadmium and copper are known to exhibi t 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 elucidat e the mechanisms of metal-toxicity. The effects on thiol metabolism by copper ions seemed to differ from that of mercury and cadmium ions. C opper ions exhibited mainly two effects that were different from those of mercury and cadmium ions. They lowered the reduced fractions of th iols and increased the release of homocysteine into the medium, wherea s mercury and cadmium ions mainly influenced the metabolism of glutath ione by increasing its synthesis. Even 0.1 mu mol/l of copper ions inc reased the release of homocysteine in HeLa cell lines. An increased ce llular concentration of glutathione and an increased release of glutat hione into the medium were observed after addition of mercury and cadm ium ions at a concentration of 1 mu mol/l, which is just above the tox icity limit in human blood. The different cell lines varied in some re spects in their response to the addition of metal ions. Cadmium ions h ad 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. Further-more, the metabolism of thi ols during basal conditions (without the addition of metal ions) diffe red 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. (C) 1998 Elsevier Science Ireland Ltd. All r ights reserved.