Comparison of the cytotoxic effects of cadmium chloride and cadmium-metallothionein in LLC-PK1 cells.
Recent studies have shown that ionic cadmium (Cd2+) can selectively damage the tight junctions between LLC-PK1 cells. The objective of the present studies was to determine if cadmium that is bound to metallothionein (Cd-Mt) can also damage the junctions between these cells. Cells on Falcon Cell Culture Inserts were exposed to Cd2+ or Cd-Mt from the apical and basolateral compartments. The integrity of cell junctions was assessed by monitoring the transepithelial electrical resistance, and cell viability was evaluated by monitoring the release of lactate dehydrogenase into the medium. Exposure to Cd2+ for 1-4 hours caused a pronounced decrease in the transepithelial resistance without affecting cell viability. By contrast, exposure to Cd-Mt had little effect on the electrical resistance until the cells began to die, which did not occur until 24-48 hours of exposure. Additional results showed that the cells accumulated Cd2+ more rapidly than Cd-Mt. These results indicate that Cd-Mt does not damage the junctions between LLC-PK1 cells, but that it can kill the cells after prolonged exposure.
Prozialeck
W C
WC
Department of Pharmacology, Midwestern University, Downers Grove, IL 60515.
Wellington
D R
DR
Lamar
P C
PC
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D019256:Cadmium Chloride; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000493:pharmacokinetics / Q000633:toxicity*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects; D007668:Kidney / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008668:Metallothionein / Q000493:pharmacokinetics / Q000633:toxicity*; D011817:Rabbits; D013552:Swine
D002712:Chlorides; C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein; D019256:Cadmium Chloride