Advancing in vitro assessment of iodide uptake inhibition: integrating a novel biotransformation pretreatment step
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F25%3A00141545" target="_blank" >RIV/00216224:14310/25:00141545 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00204-025-04034-y" target="_blank" >https://link.springer.com/article/10.1007/s00204-025-04034-y</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00204-025-04034-y" target="_blank" >10.1007/s00204-025-04034-y</a>
Alternative languages
Result language
angličtina
Original language name
Advancing in vitro assessment of iodide uptake inhibition: integrating a novel biotransformation pretreatment step
Original language description
Thyroid hormones (TH) are essential for vertebrate development, growth, and metabolism. The increasing prevalence of anthropogenic chemicals with TH-disrupting potential highlights the urgent need for advanced methods to assess their impact on TH homeostasis. Inhibition of the sodium-iodide symporter (NIS) has been identified as a key molecular initiating event disrupting the TH system across species, with significant relevance for diagnostic and therapeutic applications in various carcinomas. This study presents in vitro bioassays for evaluating the effects of compounds on iodide uptake into cells, a critical step in TH production mediated by NIS. Two novel stably transfected human cell lines overexpressing human NIS were employed along with a rat thyroid cell model FRTL-5, using colorimetric Sandell-Kolthoff (SK) reaction for iodide detection. The results from 23 model compounds demonstrate comparability across various in vitro models and radioactivity-based assays. To enhance physiological relevance, an external biotransformation system (BTS) was integrated and optimized for live-cell compatibility without inducing cytotoxicity or interfering with the assay. Compounds identified as NIS inhibitors were evaluated using the BTS-augmented assay, which revealed that metabolic activity mitigated the inhibitory effects of some chemicals. The augmented assay exhibited strong concordance with in vivo and in silico biotransformation data. Protein sequence alignment confirmed high conservation of NIS functional domains across vertebrates, reinforcing the cross-species applicability of the findings. The SK-based NIS assay, with optional BTS integration, represents a sensitive, robust, and high-throughput amendable alternative to radioactivity-based methods, for characterizing the impacts of individual compounds and complex environmental mixtures on TH homeostasis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30108 - Toxicology
Result continuities
Project
<a href="/en/project/EH22_008%2F0004644" target="_blank" >EH22_008/0004644: Saving lives through research in early cancer detection and prevention: Molecular, genomic and societal factors</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Archives of Toxicology
ISSN
0340-5761
e-ISSN
1432-0738
Volume of the periodical
99
Issue of the periodical within the volume
7
Country of publishing house
DE - GERMANY
Number of pages
17
Pages from-to
2783-2799
UT code for WoS article
001485544500001
EID of the result in the Scopus database
2-s2.0-105004921893