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 redox status and metal/thiol interactions on glutathione distribution in HeLa cell cultures. No effects were seen on glutathione distribution after the addition of different thiols, whereas the pro-oxidant copper ions affected glutathione distribution in several ways. The addition of dithiothreitol (DTT) but not the other thiols potentiated the effects of mercury ions on glutathione distribution and cell toxicity. In the presence of DTT, increased intra- and extracellular glutathione concentrations were noted already at 0.05 micromol/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 an oxidative agent (hydrogen peroxide) did not affect glutathione distribution or cell toxicity. Thus, it seems as the synergistic effects between DTT and thiol reactive agents only apply to metal ions.
Hultberg
B
B
Department of Clinical Chemistry, Institute of Laboratory Medicine, University Hospital, S-22185 Lund, Sweden.
Andersson
A
A
Isaksson
A
A
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D003300:Copper / Q000378:metabolism / Q000633:toxicity; D004229:Dithiothreitol / Q000494:pharmacology*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism*; D006367:HeLa Cells / Q000187:drug effects* / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology; D008628:Mercury / Q000378:metabolism / Q000633:toxicity*; D010084:Oxidation-Reduction; D018038:Sodium Selenite / Q000494:pharmacology
D000975:Antioxidants; D006873:Hydroquinones; D006710:Homocysteine; D003300:Copper; D006861:Hydrogen Peroxide; D008628:Mercury; D005978:Glutathione; D018038:Sodium Selenite; D004229:Dithiothreitol; D000111:Acetylcysteine; C031927:hydroquinone