Development of a non-radioactive screening assay to detect chemicals disrupting the human sodium iodide symporter activity
Bibliographic record
Abstract
Adequate concentration of iodide ions within thyroid epithelial cells, which is mediated by the sodium iodide symporter (NIS), is essential for proper thyroid hormone synthesis. Inhibition of NIS activity represents a potential mechanism by which goitrogens/toxicants can disrupt thyroid hormone physiology. It is necessary to develop a rapid, simple, inexpensive and sensitive screening assay to identify chemicals affecting NIS function. The current study compares the sensitivities of non-radioactive Sandell-Kolthoff (SK) reaction and radioactive iodide uptake (RAIU) in a previously described NIS assay. The EPAhNIS cell line (HEK293T stably transfected to over-express the human NIS) was tested with the reference NIS inhibitor (sodium perchlorate) across multiple log concentration range. The results from SK reaction in EPAhNIS cells showed similar performance to published RAIU results from the same cell line, in terms of assay screening coefficient (Z′) and variability (CV). Results from the reference chemicals tested in EPAhNIS cells revealed that SK reaction yielded IC 50 and selectivity scores consistent with those observed for RAIU. However, RAIU seems marginally more sensitive than the SK reaction, as RAIU consistently detected weaker NIS inhibitors among the test chemicals. We developed a second hNIS assay based on the MCF-7 cell line. Applying reference anions and chemicals to MCF7hNIS cells, we found that in comparison with results from EPAhNIS cells, the SK reaction with MCF7hNIS: 1) yielded similar Z′ and CV; 2) had similar IC 50 and selectivity scores for reference chemicals; 3) identified more NIS inhibitors among reference chemicals than SK reaction, but less than the RAIU assay in EPAhNIS cells. In conclusion, the SK reaction can be used with both EPAhNIS and MCF7hNIS cells to measure iodide uptake and identify NIS inhibitors, except for those presenting an extremely weak potency.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".