Dithiocarbamates are metal-chelating compounds that can exert either pro-oxidant or antioxidant effects in different situations. They have recently been found to potently inhibit apoptotic cell death, an activity attributed to their antioxidant action. However, when thymocytes were exposed to pyrrolidine dithiocarbamate, an oxidation of the glutathione pool occurred within 90 min. Longer incubation resulted in cell shrinkage, chromatin fragmentation, glutathione depletion, and eventual cell lysis, which is typical of apoptosis in these cells. These changes were inhibited by inclusion of non-permeable metal chelators in the incubation medium, suggesting that pyrrolidine dithiocarbamate exerts its toxic effect by transporting a redox-active metal into the cell. This was directly confirmed when sustained 8-fold elevations of intracellular copper were detected after addition of pyrrolidine dithiocarbamate. In agreement with this, supplementation of the incubation medium with submicromolar concentrations of copper significantly potentiated pyrrolidine dithiocarbamate toxicity. We conclude that pyrrolidine dithiocarbamate exerts a powerful pro-oxidant effect on thymocytes due to its ability to transport external redox-active copper into cells. The resulting increase in glutathione disulfide may also explain the temporary anti-apoptotic activity of this compound described in other systems.
Background: Biomarkers for mercury (Hg) exposure have frequently been used to assess exposure and risk in various groups of the general population. We have evaluated the most frequently used biomarkers and the physiology on which they are based, to explore the interindividual variations and their suitability for exposure assessment.
Background: The main forms of mercury (Hg) exposure in the general population are methylmercury (MeHg) from seafood, inorganic mercury (I-Hg) from food, and mercury vapor (Hg 0 ) from dental amalgam restorations. While the distribution of MeHg in the body is described by a one compartment model, the distribution of I-Hg after exposure to elemental mercury is more complex, and there is no biomarker for I-Hg in the brain. The aim of this study was to elucidate the relationships between on the one hand MeHg and I-Hg in human brain and other tissues, including blood, and on the other Hg exposure via dental amalgam in a fish-eating population. In addition, the use of blood and toenails as biological indicator media for inorganic and organic mercury (MeHg) in the tissues was evaluated.
There is a great need to accurately assess skin exposure to contact allergens. We have developed a technique for assessment of skin exposure to nickel, chromium and cobalt using acid wipe sampling by cellulose wipes with 1% nitric acid. Chemical analysis was performed by inductively coupled plasma mass spectrometry (ICP-MS). The recovery of nickel, chromium and cobalt from arms and palms was 93%. The analytical result is expressed in terms of mass per unit area (microg/cm(2)). The developed acid wipe sampling technique is suitable for determination of nickel, chromium and cobalt deposited on the skin. The technique may be used in workplace studies, in studies of individuals in the general population, in dermatitis patients, in identification of risk groups, as well as in developing preventive strategies and in follow-up after intervention.
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