Cellular response after mobilization of metals by diethyldithiocarbamate in rat hepatocyte cultures.
Cellular effects and mobilization of metals by diethyldithiocarbamate (DTC) were studied in primary cultures of rat hepatocytes incubated with lead acetate (PbAc), lead-diethyldithiocarbamate (Pb(DTC)2), cadmium chloride (CdCl2), cadmium-diethyldithiocarbamate (Cd(DTC)2), mercuric acetate (HgAc) and methylmercuric chloride (MeHgCl). In cells pretreated with inorganic Pb, Cd and Hg, the cellular levels of Cd and Pb were somewhat decreased or unchanged after incubation with DTC, while the cellular concentration of Hg was increased. Cells preincubated with MeHgCl showed a marked decrease in cellular Hg concentration upon DTC treatment. In Pb(DTC)2-treated cells the Pb concentration was increased when incubated with DTC, while DTC caused a decrease in Cd concentrations of cells preincubated with Cd(DTC)2. The activity of alcohol dehydrogenase (ADH) in cells incubated with CdCl2, Cd(DTC)2 and HgAc was significantly decreased. In Hg-treated cells the ADH activity was further decreased after incubation with DTC, whereas the activity in Cd-treated cells recovered gradually after incubation with increasing concentrations of DTC. The activity of the enzyme delta-aminolevulinic acid dehydratase (ALAD) was significantly inhibited in cells treated with PbAc and Pb(DTC)2, but could be restored to 80% and to almost 100%, respectively, of control activity after incubation with DTC. It is suggested that, in the absence of excess DTC, a decomposition of Pb(DTC)2 takes place after penetration into the cell, resulting in inhibition of ALAD by the released Pb. In the presence of excessive amounts of DTC, the equilibrium is shifted towards Pb(DTC)2 and Pb in the complex form is not available for ALAD. These studies suggest that DTC decreases cellular effects of Pb and Cd despite unchanged or even increased cellular concentrations of the metals, while the antidotal efficacy of DTC on inorganic Hg toxicity seems to be of low value.
Hellström-Lindahl
E
E
Toxicology Laboratory, National Food Administration, Uppsala, Sweden.
Oskarsson
A
A
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity; D002478:Cells, Cultured; D002614:Chelating Agents; D004050:Ditiocarb / Q000494:pharmacology* / Q000627:therapeutic use; D007854:Lead / Q000378:metabolism / Q000633:toxicity; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000378:metabolism / Q000633:toxicity; D008670:Metals / Q000378:metabolism / Q000633:toxicity*; D011041:Poisoning / Q000188:drug therapy; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002614:Chelating Agents; D008670:Metals; D002104:Cadmium; D007854:Lead; D004050:Ditiocarb; D000426:Alcohol Dehydrogenase; D000623:Porphobilinogen Synthase; D008628:Mercury