Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells.
Perchlorate blocks thyroidal iodide transport in a dose-dependent manner. The human sodium/iodide symporter (NIS) has a 30-fold higher affinity for perchlorate than for iodide. However, active transport of perchlorate into thyroid cells has not previously been demonstrated by direct measurement techniques. To demonstrate intracellular perchlorate accumulation, we incubated NIS-expressing FRTL-5 rat thyroid cells in various concentrations of perchlorate, and we used a sensitive ion chromatography tandem mass spectrometry method to measure perchlorate accumulation in the cells. Perchlorate caused a dose-related inhibition of 125-iodide uptake at 1-10 microM. The perchlorate content from cell lysate was analyzed, showing a higher amount of perchlorate in cells that were incubated in medium with higher perchlorate concentration. Thyroid-stimulating hormone increased perchlorate uptake in a dose-related manner, thus supporting the hypothesis that perchlorate is actively transported into thyroid cells. Incubation with nonradiolabeled iodide led to a dose-related reduction of intracellular accumulation of perchlorate. To determine potential toxicity of perchlorate, the cells were incubated in 1 nM to 100 microM perchlorate and cell proliferation was measured. Even the highest concentration of perchlorate (100 microM) did not inhibit cell proliferation after 72 h of incubation. In conclusion, perchlorate is actively transported into thyroid cells and does not inhibit cell proliferation.
Tran
Neil
N
Endocrine Research Laboratory, Veterans Affairs Medical Center West Los Angeles, University of California Los Angeles School of Medicine, Los Angeles, CA 90073, USA.
Valentín-Blasini
Liza
L
Blount
Benjamin C
BC
McCuistion
Caroline Gibbs
CG
Fenton
Mike S
MS
Gin
Eric
E
Salem
Andrew
A
Hershman
Jerome M
JM
D000818:Animals; D001667:Binding, Competitive; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007454:Iodides / Q000493:pharmacokinetics; D010472:Perchlorates / Q000493:pharmacokinetics*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D027981:Symporters / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology*; D000099209:Sodium-Iodide Symporters
D007454:Iodides; D010472:Perchlorates; D027981:Symporters; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters; C494474:perchlorate