Relative Potencies and Additivity of Perchlorate, Thiocyanate, Nitrate, and Iodide on the Inhibition of Radioactive Iodide Uptake by the Human Sodium Iodide Symporter

The presence of perchlorate (ClO4 -) in some U.S. drinking water supplies has raised concern about potential adverse thyroidal health effects, because ClO4 - is known to competitively inhibit iodide uptake at the sodium iodide symporter (NIS). Humans are nutritionally and environmentally exposed to other competitive inhibitors of iodide uptake, including thiocyanate (SCN-) and nitrate (NO3 -). The joint inhibiting effects of these three anions was studied by exposing Chinese hamster ovary cells stably expressing human NIS to varying concentrations of each anion separately, and in combination, and conducting measurements of 125I- uptake. The entire data set was fit to a single Hill equation using maximum likelihood. The relative potency of ClO4 - to inhibit 125I- uptake at the NIS was found to be 15, 30 and 240 times that of SCN-, I-, and NO3 - respectively on a molar concentration basis, with no evidence of synergism. These results are consistent with a common mode of action by these anions of simple comp...