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 (CIO4-) in some U.S. drinking water supplies has raised concern about potential adverse thyroidal health effects, because CIO4- 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 I-125(-) uptake. The entire data set was fit to a single Hill equation using maximum likelihood. The relative potency of CIO4- to inhibit I-125(-) 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 competitive interaction, in which a concentration of any one of CIO4- SCN-, and NO3-, occurring either individually or as part of a mixture of the three anions, is indistinguishable from a concentration or dilution of either one of the remaining two ions in inhibiting iodine uptake at the NIS.