Use of the thyrocyte sodium iodide symporter as the basis for a perchlorate cell-based assay

Abstract

Perchlorates are strong oxidants widely employed in military and civilian energetic materials and recently have been scrutinized as persistent environmental pollutants. The perchlorate anion, ClO₄⁻, is a well-known and potent competitive inhibitor of iodide transport by the sodium iodide symporter (NIS) expressed in the basolateral membranes of thyroid follicular cells (thyrocytes). Iodide uptake by thyroid follicular cells is rapid and reproducible. The competitive radiotransporter assay in this study shows promise as a rapid and convenient method to assay for ClO₄⁻ in water samples at the nM level. This work describes the initial efforts to define the assay conditions that enhance NIS selectivity for ClO₄⁻. Experiments of 10 min co-incubation of ClO₄⁻ and ¹²⁵I⁻ demonstrate a more significant effect on ¹²⁵I⁻transport, with a quantifiable ClO₄⁻ concentration range of 50 nM (5 ppb) to 2 μM (200 ppb), and IC₅₀ of 180 nM (18 ppb), nearly three-fold lower than previous reports. Since the IC₅₀ in our assay for other known competitor anions (SCN⁻, ClO₃⁻, NO₃⁻) remains unchanged from previous research, the increased sensitivity for ClO₄⁻ also produces a three-fold enhancement in selectivity. In addition to the possible applicability of the thyrocyte to the development of a cellular perchlorate biosensor, we propose that the high affinity of the NIS for ClO₄⁻ also creates the potential for exploiting this membrane protein as a selective, sensitive, and broadly applicable biomechanical mechanism for controlled movement and concentration of perchlorate.