The carcinogenic potency of nickel compounds depends on the ability of nickel ions to enter target cells. The presumptive preventive potential of several metals against nickel-induced cancer may depend on their capacity to inhibit nickel uptake. Surface binding and uptake of 63Ni2+ in immortalized human kidney epithelial (IHKE) cells suspended in a salts/glucose minimal medium was studied at 0.085 mM nickel. Nickel uptake, after a rapid phase of about 2 h, continued at a slower rate for several hours. Nicardipine (50 microM) decreased uptake to about 25% of control values. Ionomycin (3 microM) increased uptake 4- to 5-fold. Nickel uptake into IHKE cells was decreased by metal cations. In the absence of ionomycin, this effect followed the order Zn > Cd > Co > Mn > Mg >> Ca. In the presence of ionomycin the order was Zn > Cd > Co > Mn >> Ca > Mg. These metals inhibited uptake more strongly than binding to the cell surface. However, Co2+ reduced surface binding strongly in ionomycin-potentiated uptake. With no ionomycin present, 0.15 mM Zn2+, 1 mM Mn2+, 4 mM Mg2+ or 70 mM Ca2+ caused 80-85% inhibition of nickel uptake. In the absence of ionomycin, calcium was a weaker inhibitor of nickel uptake than magnesium. In the presence of ionomycin, calcium was a stronger inhibitor than magnesium. The results indicate that nickel can be taken up through calcium channels in IHKE cells. It is suggested that ionomycin-potentiated transport mechanisms, under the conditions applied, are different from normal mechanisms of transport functioning in the absence of ionomycin. Different metals, essential and non-essential, seem to be inhibitors or competitors for the transport mechanisms.
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Refsvik et al. (1995) studied this question.