Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol

In the present study, we have investigated the effects of extracellular red ox status and metal/thiol interactions on glutathione distribution in HeLa cell cultures. No effects were seen on glutathione distribution after the a ddition of different thiols, whereas the pro-oxidant copper ions affected g lutathione distribution in several ways. The addition of dithiothreitol (DT T) but not the other thiols potentiated the effects of mercury ions on glut athione distribution and cell toxicity. In the presence of DTT, increased i ntra- and extracellular glutathione concentrations were noted already at 0. 05 mu mol/l, which was below the previously reported toxicity threshold for mercury ions in blood. Likewise DTT potentiated the effects of copper ions on glutathione distribution and cell toxicity, whereas the addition of DTT to cell cultures with a non-metal thiol reactive agent (hydroquinone) or a n oxidative agent (hydrogen peroxide) did not affect glutathione distributi on or cell toxicity. Thus, it seems as the synergistic effects between DTT and thiol reactive agents only apply to metal ions. (C) 2001 Elsevier Scien ce Ireland Ltd. All rights reserved.