Increased availability of mercury in rat hepatocytes by complex formation with diethyldithiocarbamate.
The availability of different chemical forms of mercury (Hg) was studied in primary cultures of rat hepatocytes incubated with mercuric acetate (HgAc), mercuric diethyldithiocarbamate (Hg(DTC)2) or methyl mercuric chloride (MeHgCl), labelled with 203Hg. The uptake of Hg was linearly related to the concentration in the medium and increased in the order Hg(DTC)2 greater than MeHgCl greater than HgAc when similar concentrations of Hg were used. A maximum concentration of Hg was reached after 4 h incubation with Hg(DTC)2 while incubation with HgAc and MeHgCl resulted in a slow continuous accumulation of Hg for up to 24 h. Hg added as HgAc was bound to proteins in the incubation medium to a greater extent than Hg added as Hg(DTC)2 or MeHgCl. Differences in affinity to the medium, as well as in lipophilicity, may partly explain the observed differential uptake of these Hg compounds. The enzyme alcohol dehydrogenase was inhibited by HgAc and Hg(DTC)2 to a similar extent at comparable cellular concentrations of Hg. On the other hand, glutathione reductase was inhibited to a higher degree by HgAc than by Hg(DTC)2, indicating that Hg(DTC)2 remains at least temporarily in the complexed form and that the enzyme is less susceptible to Hg in this form. Both enzymes were much less susceptible to MeHgCl than to HgAc or Hg(DTC)2. The results from the present study indicate that diethyldithiocarbamate can increase the transport of Hg across the cellular membrane by complex formation with Hg and thereby increase the toxicity of Hg.
Hellström-Lindahl
E
E
Toxicology Laboratory, National Food Administration, Uppsala, Sweden.
Oskarsson
A
A
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004050:Ditiocarb / Q000378:metabolism* / Q000633:toxicity; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008628:Mercury / Q000378:metabolism* / Q000633:toxicity; D008767:Methylmercury Compounds / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D008767:Methylmercury Compounds; D004050:Ditiocarb; D000426:Alcohol Dehydrogenase; D005980:Glutathione Reductase; D008628:Mercury; C029823:mercuric acetate