Sodium-iodide symporter positive cells after intracellular uptake of 99mTc versus α-emitter 211At

2012 ◽  
Vol 51 (05) ◽  
pp. 170-178 ◽  
Author(s):  
M. Wendisch ◽  
R. Freudenberg ◽  
R. Runge ◽  
L. Oehme ◽  
G.J. Meyer ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Cell Model ◽  
Absorbed Dose ◽  
Thyroid Cell ◽  
Intracellular Uptake ◽  
Sodium Iodide Symporter ◽  
Radionuclide Distribution ◽  
Rat Thyroid ◽  
The Impact

SummaryPurpose: We evaluated the DNA damaging potential of Auger electrons emitted in the decay of 99mTc compared to α-particles of 211At. Material and methods: The impact of 99mTc and 211At was monitored in a NIS-expressing rat thyroid cell model PC Cl3 with varying, yet defined intra- and extracellular radionuclide distribution (using ± perchlorate). The radiotoxicity of 99mTc and 211At was studied by the comet assay under neutral and alkaline conditions and colony formation. Results: In the presence of perchlorate, the radioactivity yielding 37 % cellular survival, A37, was estimated to be (0.27 ± 0.02) MBq/ml and (450 ± 30) MBq/ml for 211At and 99mTc, respectively. In absence of perchlorate, cellular radiotracer uptake was similar for both radionuclides (2.2 %, 2.7 %), yet the A37 was reduced by 82% for the α-emitter and by 95 % for 99mTc. Cellular dose increased by a factor of 5 (211At) and 38 (99mTc). Comet assays revealed an increased DNA damage after intracellular uptake of both radiotracers. Conclusions: The data indicate damage to the cell to occur from absorbed dose without recognizable contribution from intracellular heterogeneity of radionuclide distribution. Comet assay under alkaline and neutral conditions did not reveal any shift to more complex DNA damage after radionuclide uptake. Cellular uptake of 99mTc and 211At increased cellular dose and reduced clonogenic survival.

scholarly journals Differential Interactions between Th1/Th2, Th1/Th3, and Th2/Th3 Cytokines in the Regulation of Thyroperoxidase and Dual Oxidase Expression, and of Thyroglobulin Secretion in Thyrocytes in Vitro

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1534-1542 ◽  
Author(s):  
Sylvie Poncin ◽  
Benoit Lengelé ◽  
Ides M. Colin ◽  
Anne-Catherine Gérard
Keyword(s):  
Thyroid Function ◽  
Interferon Γ ◽  
Thyroid Cell ◽  
Dual Oxidase ◽  
Th1 Cytokine ◽  
Glandular Atrophy ◽  
Rat Thyroid ◽  
Th1 Cytokines ◽  
The Impact

Hypothyroidism, together with glandular atrophy, is the usual outcome of destructive autoimmune thyroiditis. The impairment in the thyroid function results either from cell destruction or from Th1 cytokine-induced alteration in hormonogenesis. Here, we investigated the impact of the local immune context on the thyroid function. We used two rat thyroid cell lines (PCCL3 and FRTL-5) and human thyrocytes incubated with IL-1α/interferon (IFN) γ together with IL-4, a Th2 cytokine, or with TGF-β, or IL-10, two Th3 cytokines. We first observed that IL-4 totally blocked IL-1α/interferon γ-induced alteration in dual oxidase and thyroperoxidase expression, and in thyroglobulin secretion. By contrast, TGF-β and IL-10 had no such effect. They rather repressed thyrocyte function as do Th1 cytokines. In addition, IL-4 blocked IL-10-induced repression of thyrocyte function, but not that induced by TGF-β. In conclusion, Th1 cytokine- and IL-10-induced local inhibitory actions on thyroid function can be totally overturned by Th2 cytokines. These data provide new clues about the influence of the immune context on thyrocyte function.

scholarly journals Regulation of the sodium iodide symporter by iodide in FRTL-5 cells

2001 ◽  
pp. 139-144 ◽  
Author(s):  
PH Eng ◽  
GR Cardona ◽  
MC Previti ◽  
WW Chin ◽  
LE Braverman
Keyword(s):  
Sodium Iodide ◽  
Cell Model ◽  
High Plasma ◽  
Northern Analysis ◽  
Thyroid Cell ◽  
Transcriptional Level ◽  
Sodium Iodide Symporter ◽  
Iodide Transport ◽  
Excess Iodide

OBJECTIVE: The acute decrease in iodide organification in the thyroid in response to excess iodide is termed the acute Wolff-Chaikoff effect and normal organification resumes in spite of continued high plasma iodide concentrations (escape from the acute Wolff-Chaikoff effect). We have recently reported that large doses of iodide given to rats chronically decrease the sodium/iodide symporter (NIS) mRNA and protein, suggesting that escape is due to a decrease in NIS and subsequent iodide transport. We have now studied the effect of excess iodide on NIS in FRTL-5 cells to further explore the mechanisms whereby excess iodide decreases NIS. DESIGN: FRTL-5 cells were employed and were incubated in the presence or absence of various concentrations of iodide. NIS mRNA and protein and the turnover of NIS were assessed. METHODS: NIS mRNA was measured by Northern analysis, NIS protein by Western analysis and NIS turnover by pulse-chase labeling experiments. RESULTS: Iodide (10(-) mol/l) had no effect on NIS mRNA in FRTL-5 cells at 24 and 48 h compared with cells cultured in the absence of iodide. However, excess iodide decreased NIS protein by 50% of control values at 24 h and by 70% at 48 h. This effect of iodide was dose dependent. Pulse-chase experiments demonstrated that there was no effect of iodide on new NIS protein synthesis and that the turnover of NIS protein in the presence of iodide was 27% faster than in the absence of added iodide. CONCLUSIONS: Excess iodide does not decrease NIS mRNA in FRTL-5 cells but does decrease NIS protein, suggesting that in this in vitro thyroid cell model iodide modulates NIS, at least in part, at a post-transcriptional level. This iodide-induced decrease in NIS protein appears to be due, at least partially, to an increase in NIS protein turnover.

scholarly journals Bisphenol A increases hydrogen peroxide generation by thyrocytes both in vivo and in vitro

2018 ◽  
Vol 7 (11) ◽  
pp. 1196-1207 ◽  
Author(s):  
Maurício Martins da Silva ◽  
Lueni Lopes Felix Xavier ◽  
Carlos Frederico Lima Gonçalves ◽  
Ana Paula Santos-Silva ◽  
Francisca Diana Paiva-Melo ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Bisphenol A ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Iodide Uptake ◽  
Hydrogen Peroxide Generation ◽  
Rat Thyroid ◽  
The Impact

Bisphenol A (BPA) is the most common monomer in polycarbonate plastics and an endocrine disruptor. Though some effects of BPA on thyroid hormone (TH) synthesis and action have been described, the impact of this compound on thyroid H2O2 generation remains elusive. H2O2 is a reactive oxygen species (ROS), which could have deleterious effect on thyrocytes if in excess. Therefore, herein we aimed at evaluating the effect of BPA exposition both in vivo and in vitro on H2O2 generation in thyrocytes, besides other essential steps for TH synthesis. Female Wistar rats were treated with vehicle (control) or BPA 40 mg/kg BW for 15 days, by gavage. We then evaluated thyroid iodide uptake, mediated by sodium-iodide symporter (NIS), thyroperoxidase (TPO) and dual oxidase (DOUX) activities (H2O2 generation). Hydrogen peroxide generation was increased, while iodide uptake and TPO activity were reduced by BPA exposition. We have also incubated the rat thyroid cell line PCCL3 with 10−9 M BPA and evaluated Nis and Duox mRNA levels, besides H2O2 generation. Similar to that found in vivo, BPA treatment also led to increased H2O2 generation in PCCL3. Nis mRNA levels were reduced and Duox2 mRNA levels were increased in BPA-exposed cells. To evaluate the importance of oxidative stress on BPA-induced Nis reduction, PCCL3 was treated with BPA in association to N-acetylcysteine, an antioxidant, which reversed the effect of BPA on Nis. Our data suggest that BPA increases ROS production in thyrocytes, what could lead to oxidative damage thus possibly predisposing to thyroid disease.

Primary DNA Damage Assessed With the Comet Assay and Comparison to the Absorbed Dose of Diagnostic X-rays in Children

2009 ◽  
Vol 28 (5) ◽  
pp. 405-416 ◽  
Author(s):  
Đurđica Milković ◽  
Vera Garaj-Vrhovac ◽  
Mária Ranogajec-Komor ◽  
Saveta Miljanić ◽  
Goran Gajski ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Absorbed Dose ◽  
Peripheral Blood Lymphocytes ◽  
X Rays ◽  
X Ray ◽  
Before And After ◽  
The Individual ◽  
Dose Measurements ◽  
Posterior Anterior

The aim of this work is to assess DNA damage in peripheral blood lymphocytes of children prior to and following airway X-ray examinations of the chest using the alkaline comet assay and to compare data with the measured absorbed dose. Twenty children with pulmonary diseases, between the ages of 5 and 14 years, are assessed. Absorbed dose measurements are conducted for posterior–anterior projection on the forehead, thyroid gland, gonads, chest, and back. Doses are measured using thermoluminescent and radiophotoluminescent dosimetry systems. Differences between tail lengths, tail intensity, and tail moments as well as for the long-tailed nuclei before and after exposures are statistically significant and are dependent on the individual. The results demonstrate the usefulness of the comet assay as a measure of X-ray damage to lymphocytes in a clinical setting. Doses measured with both dosimeters show satisfactory agreement (0.01 mSv) and are suitable for dosimetric measurements in X-ray diagnostics.

scholarly journals Interspecies variation in DNA damage induced by pollution

2014 ◽  
Vol 60 (2) ◽  
pp. 308-321 ◽  
Author(s):  
Claudia Sebbio ◽  
Claudio Carere ◽  
Giuseppe Nascetti ◽  
Bruno Bellisario ◽  
Pasquale Mosesso ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Dna Damage ◽  
Power Plant ◽  
Comet Assay ◽  
Tissue Concentration ◽  
Central Italy ◽  
Rana Esculenta ◽  
Chemical Pollution ◽  
Aphanius Fasciatus ◽  
The Impact

Abstract The choice of a suitable species to translate pollution signals into a quantitative monitor is a fundamental step in biomonitoring plans. Here we present the results of three years of biomonitoring at a new coal power plant in central Italy using three different aquatic and terrestrial wildlife species in order to compare their reliability as sentinel organisms for genotoxicity. The comet assay was applied to the common land snail Helix spp., the lagoon fish Aphanius fasciatus, and the green frog Rana esculenta sampled in the area potentially exposed to the impact of the power station. The tissue concentration of some expected pollutants (As, Cd, Ni, Pb, Cr) was analysed in parallel samples collected in the same sampling sites. The three species showed different values in the comet assay (Tail Intensity) and different accumulation profiles of heavy metals. Aphanius fasciatus showed an increasing genotoxic effect over time that paralleled the temporal increase of the heavy metals, especially arsenic, and the highest correlation between heavy metals and DNA damage. Helix spp. showed levels of damage inversely related to the distance from the source of pollution and in partial accordance with the total accumulation of trace elements. On the contrary, Rana esculenta showed a low capability to accumulate metals and had inconsistent results in the comet test. The fish appeared to be the most efficient and sensitive species in detecting chemical pollution. Overall, both the fish and the snail reflected a trend of increasing pollution in the area surrounding the power plant across time and space.

scholarly journals Prevention of DNA Double-Strand Breaks Induced by Radioiodide-131I in FRTL-5 Thyroid Cells

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1130-1135 ◽  
Author(s):  
Jerome M. Hershman ◽  
Armen Okunyan ◽  
Yelena Rivina ◽  
Sophie Cannon ◽  
Victor Hogen
Keyword(s):  
Nuclear Reactor ◽  
Cell Model ◽  
Fragile Sites ◽  
Early Event ◽  
Thyroid Cell ◽  
Sodium Iodide Symporter ◽  
Dna Double Strand Breaks ◽  
Dna Breaks ◽  
Thyroid Cells ◽  
Dna Dsbs

Radioiodine-131 released from nuclear reactor accidents has dramatically increased the incidence of papillary thyroid cancer in exposed individuals. The deposition of ionizing radiation in cells results in double-strand DNA breaks (DSB) at fragile sites, and this early event can generate oncogenic rearrangements that eventually cause cancer. The aims of this study were to develop a method to show DNA DSBs induced by 131I in thyroid cells; to test monovalent anions that are transported by the sodium/iodide symporter to determine whether they prevent 131I-induced DSB; and to test other radioprotective agents for their effect on irradiated thyroid cells. Rat FRTL-5 thyroid cells were incubated with 131I. DSBs were measured by nuclear immunofluorescence using antibodies to p53-binding protein 1 or γH2AX. Incubation with 1–10 μCi 131I per milliliter for 90 min resulted in a dose-related increase of DSBs; the number of DSBs increased from a baseline of 4–15% before radiation to 65–90% after radiation. GH3 or CHO cells that do not transport iodide did not develop DSBs when incubated with 131I. Incubation with 20–100 μm iodide or thiocyanate markedly attenuated DSBs. Perchlorate was about 6 times more potent than iodide or thiocyanate. The effects of the anions were much greater when each was added 30–120 min before the 131I. Two natural organic compounds recently shown to provide radiation protection partially prevented DSBs caused by 131I and had an additive effect with perchlorate. In conclusion, we developed a thyroid cell model to quantify the mitogenic effect of 131I. 131I causes DNA DSBs in FRTL-5 cells and had no effect on cells that do not transport iodide. Perchlorate, iodide, and thiocyanate protect against DSBs induced by 131I.

scholarly journals Cloning of a functional promoter of the human sodium/iodide-symporter gene

1998 ◽  
Vol 331 (2) ◽  
pp. 359-363 ◽  
Author(s):  
Michael BEHR ◽  
Thomas L. SCHMITT ◽  
Celia R. ESPINOZA ◽  
Ulrich LOOS
Keyword(s):  
Sodium Iodide ◽  
Chinese Hamster ◽  
Tata Box ◽  
Start Codon ◽  
Thyroid Cell ◽  
Sodium Iodide Symporter ◽  
Untranslated Sequence ◽  
Thyroid Cell Line ◽  
Lower Extent ◽  
Rat Thyroid

We have cloned and sequenced genomic DNA from a human library extending 1300 bp upstream the 5´-untranslated sequence of the cDNA coding for the sodium/iodide symporter. In transient transfection assays this sequence exhibited promoter activity, which could be confined to nucleotides -443 to -395 relative to the ATG start codon. This minimal promoter, including a putative GC- and TATA- box, was preferentially activated in the rat thyroid cell line FRTL-5, but was also active in non-thyroidal cells, such as COS-7 and Chinese-hamster ovary, albeit to a markedly lower extent.

Acrylamide, an in vivo thyroid carcinogenic agent, induces DNA damage in rat thyroid cell lines and primary cultures

2006 ◽  
Vol 257-258 ◽  
pp. 6-14 ◽  
Author(s):  
V. Chico Galdo ◽  
C. Massart ◽  
L. Jin ◽  
V. Vanvooren ◽  
P. Caillet-Fauquet ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Primary Cultures ◽  
Thyroid Cell ◽  
Carcinogenic Agent ◽  
Rat Thyroid

scholarly journals Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA Damage

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1930
Author(s):  
Vanessa Valdiglesias ◽  
Natalia Fernández-Bertólez ◽  
Carlota Lema-Arranz ◽  
Raquel Rodríguez-Fernández ◽  
Eduardo Pásaro ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Metal Oxide ◽  
Oxidative Dna Damage ◽  
Metal Oxide Nanoparticles ◽  
Consumer Products ◽  
Specific Regulation ◽  
Vitro Model ◽  
The Impact

Metal oxide nanoparticles (NPs) have a wide variety of applications in many consumer products and biomedical practices. As a result, human exposure to these nanomaterials is highly frequent, becoming an issue of concern to public health. Recently, human salivary leucocytes have been proposed as an adequate non-invasive alternative to peripheral blood leucocytes to evaluate genotoxicity in vitro. The present study focused on proving the suitability of salivary leucocytes as a biomatrix in the comet assay for in vitro nanogenotoxicity studies, by testing some of the metal oxide NPs most frequently present in consumer products, namely, titanium dioxide (TiO2), zinc oxide (ZnO), and cerium dioxide (CeO2) NPs. Primary and oxidative DNA damage were evaluated by alkaline and hOGG1-modified comet assay, respectively. Any possible interference of the NPs with the methodological procedure or the hOGG1 activity was addressed before performing genotoxicity evaluation. Results obtained showed an increase of both primary and oxidative damage after NPs treatments. These data support the use of salivary leucocytes as a proper and sensitive biological sample for in vitro nanogenotoxicity studies, and contribute to increase the knowledge on the impact of metal oxide NPs on human health, reinforcing the need for a specific regulation of the nanomaterials use.

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