Studies of cadmium chelator efficacy using mammalian cell cultures

An experimental system is presented for the assessment of the efficacy of chelating agents against cadmium. Mammalian cells in vitro can be employed to screen compounds that modify metal uptake, metal toxicity and metal mobilization from metal-loaded cells and can thus identify likely, or exclude unsuitable, candidates for the therapy or prevention of metal intoxification. Examples are given of possible cadmium antidotes. As a first step the toxicity of the chelating agents for different cells lines did not show appreciable differences. For the testing of the chelating agents a highly Cd-sensitive cell line was selected, which also exhibited a well measurable Cd uptake. The influence of the chelators on cadmium incorporation was studied and correlated with the results of experiments where the metal and the antidotes were simultaneously applied. Chelating agents causing reduced Cd uptake generally also depressed Cd toxicity. However, two or the compounds which led to increased cellular Cd incorporation did not modify metal cytotoxicity in a corresponding fashion. These paradoxical findings indicate complex interactions between chelators, metals and cells. Finally, cells were pre-treated with Cd and exposed to chelating agents. Only one of the substances tested, i.e., diethyldithiocarbamate, was capable of affecting Cd release from the cells. The results obtained with this model system show good agreement with finding reported in vivo.