| 1. |
- Lundh, Charlotta, 1977, et al.
(författare)
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Radiation-induced thyroid stunning: differential effects of (123)I, (131)I, (99m)Tc, and (211)At on iodide transport and NIS mRNA expression in cultured thyroid cells.
- 2009
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505. ; 50:7, s. 1161-7
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Tidskriftsartikel (refereegranskat)abstract
- Recent clinical and experimental data demonstrate that thyroid stunning is caused by previous irradiation and may influence the efficacy of (131)I radiation therapy of thyroid cancer and possibly hyperthyroidism. To avoid stunning, many clinics have exchanged (131)I for (123)I for pretherapeutic diagnostic imaging and dose planning. Furthermore, recent in vitro studies indicate that (131)I irradiation reduces iodide uptake by downregulating the expression of the sodium iodide symporter (NIS). The rationale for this study was therefore to study effects on iodide transport and NIS messenger RNA (mRNA) expression in thyrocytes exposed to both (123)I and (131)I in addition to some other potentially interesting radionuclides. METHODS: Thyrotropin-stimulated thyroid cell monolayers were exposed to 0.5 Gy of (123)I, (131)I, (99m)Tc, or (211)At, all being radionuclides transported via NIS, in the culture medium for 6 h, or to various absorbed doses of (123)I or (131)I for 48 h. NIS mRNA expression was analyzed using quantitative reverse-transcriptase polymerase chain reaction. RESULTS: Iodide transport and NIS mRNA expression were reduced by all radionuclides. At the same absorbed dose, iodide transport was reduced the most by (211)At, followed by (123)I and (99m)Tc (equally potent), whereas (131)I was least effective. The onset of NIS downregulation was rapid (<1 d after irradiation) in cells exposed to (123)I or (211)At and was delayed in cells irradiated with (131)I or (99m)Tc. Iodide transport and NIS expression were recovered only for (211)At. (123)I reduced the iodine transport and the NIS mRNA expression more efficiently than did (131)I at an equivalent absorbed dose, with a relative biological effectiveness of about 5. CONCLUSION: The stunning effect per unit absorbed dose is more severe for (123)I than for (131)I. Despite the lower absorbed dose per unit activity for (123)I than for (131)I, stunning by (123)I cannot be excluded in patients. The degree to which iodide transport capacity and NIS mRNA expression are reduced seems to be related to the biological effectiveness of the type of radiation delivering the absorbed dose to the target, with (211)At (which has the highest relative biological effectiveness) causing the highest degree of stunning per unit absorbed dose in the present study.
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| 2. |
- Lyckesvärd, Madeleine Nordén, et al.
(författare)
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Linking loss of sodium-iodide symporter expression to DNA damage
- 2016
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 344:1, s. 120-131
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (< 1 nM) calicheamicin blocked NIS mRNA expression and transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress. (C) 2016 Elsevier Inc. All rights reserved.
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| 3. |
- Postgård, Per, et al.
(författare)
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Stunning of iodide transport by (131)I irradiation in cultured thyroid epithelial cells.
- 2002
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 43:6, s. 828-34
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Tidskriftsartikel (refereegranskat)abstract
- The existence of thyroid stunning (i.e., inhibited thyroidal iodide uptake after administration of diagnostic amounts of (131)I) is controversial and is currently a subject of debate. To our knowledge, the stunning phenomenon has not been investigated previously in vitro. METHODS: Growth-arrested porcine thyroid cells that formed a tight and polarized monolayer in a bicameral chamber were irradiated with 3-80 Gy (131)I present in the surrounding culture medium for 48 h. The iodide transport capacity after irradiation was evaluated 3 d later by measuring the transepithelial (basal to apical) flux of trace amounts of (125)I. RESULTS: The basal-to-apical (125)I transport decreased with increasing absorbed dose acquired from (131)I; a nearly 50% reduction was observed already at 3 Gy. Stable iodide at the same molarity as (131)I (10(-8) mol/L) had no effect on the (125)I transport. Cell number and epithelial integrity were not affected by irradiation. CONCLUSION: Stunning of iodide transport is detected after (131)I irradiation of cultured thyroid cells. The degree of inhibition of transport is dependent on the absorbed dose.
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