Role of trace elements in cadmium chloride uptake in hepatoma cell lines

Cadmium coexists with other metals in various products. Releases of cadmium in the environment occur in parallel to the release of other metals including copper, iron and zinc which also have an essential role in human homeostasis as they participate in various biochemical pathways. We studied the interaction of iron, copper, zinc and calcium channel blockers (nifedipine and verapamil) with cadmium chloride in two hepatoma cell lines (HepG2 and HTC cells) in order to determine if these trace elements can affect CdCl(2) uptake and interfere with its toxicity. Both cell lines were initially exposed to CdCl(2) (0-200 microM) for 2h and the uptake of the metal was determined. Cadmium chloride uptake by HepG2 and HTC cells shows an increase with increasing doses of the metal. Cells were also pretreated with 100 uM of FeCl(2) or ZnCl(2) or CuCl(2) or with a nifedipine/verapamil (100 uM) mixture for 2h and then exposed to 200 uM CdCl(2) for 1h in the presence of the trace elements. The uptake of CdCl(2) was determined as well as the membrane integrity (LDH leakage assay), the cell viability (neutral red assay) and cell proliferation (protein assay). Zinc and calcium channel blockers inhibited the uptake of cadmium chloride by both cell lines. On the other hand iron loading resulted in increased uptake of CdCl(2) by both cell lines whereas copper loading increased the uptake of cadmium chloride from HTC cells and inhibited the uptake by HepG2 cells. These findings are of importance when the effects of cadmium on living organisms are examined since co-exposure to cadmium and other metals can occur.