Response of rat hepatocyte cultures to cadmium chloride and cadmium-diethyldithiocarbamate.
Cellular effects of cadmium (Cd) were studied in primary cultures of rat hepatocytes incubated with cadmium chloride (CdCl2) or cadmium-diethyldithiocarbamate (Cd(DTC)2), labelled with 109Cd. The lipid-soluble complex Cd(DTC)2 was rapidly taken up into the cells and a maximal concentration was reached after 4 h incubation. On the other hand, incubation with CdCl2 resulted in a slow, continuous accumulation of Cd for up to 20 h. Cd was found to be associated with proteins to a higher extent when added to the incubation medium as CdCl2 than when added as Cd(DTC)2, which in addition to differences in lipophilicity of the Cd compounds partly explains the differences in Cd uptake. Subcellular distribution studies showed that a significantly higher proportion of Cd was associated with the total particulates fraction in cells after incubation with Cd(DTC)2 compared to CdCl2 (32 and 19%, respectively). The activities of glutathione reductase and succinic dehydrogenase were inhibited to a similar extent by the 2 Cd compounds. Alcohol dehydrogenase was more strongly affected by CdCl2 than by Cd(DTC)2, although the uptake of Cd was 3-4 times higher in cells incubated with Cd(DTC)2 than in those incubated with CdCl2. The results from the present study show that DTC can increase the transport of Cd into the cell by complex formation with Cd. Compared to CdCl2 the Cd(DTC)2 complex was less toxic as indicated by the biochemical parameters used.
Hellström-Lindahl
E
E
Toxicology Laboratory, National Food Administration, Uppsala, Sweden.
Oskarsson
A
A
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics* / Q000633:toxicity; D019256:Cadmium Chloride; D002478:Cells, Cultured / Q000187:drug effects; D004050:Ditiocarb / Q000493:pharmacokinetics* / Q000633:toxicity; D005980:Glutathione Reductase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013385:Succinate Dehydrogenase / Q000378:metabolism
D002104:Cadmium; D004050:Ditiocarb; D000426:Alcohol Dehydrogenase; D013385:Succinate Dehydrogenase; D005980:Glutathione Reductase; D019256:Cadmium Chloride