The Molecular Effect of Diagnostic Absorbed Doses from 131I on Papillary Thyroid Cancer Cells In Vitro.

Mariusz Stasiołek,Bolesław Karwowski,Zbigniew Adamczewski,Marek Dedecjus,Bartosz Puła,Przemysław Śliwka,Andrzej Lewiński,Anna Merecz-Sadowska

doi:10.3390/molecules22060993

Abstract

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of 131I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake—the phenomenon called “thyroid stunning”. We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to 131I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations (p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of 131I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology.

Highlights

IntroductionThe unique features of differentiated thyroid cancer (DTC) cells are: ability to take up iodine, presence of the thyroid-stimulating hormone (TSH) receptor, synthesis of thyroglobulin (Tg) and, in some cases, synthesis of thyroid hormones
Thyroid cancer represents the most frequent endocrine malignancy, with differentiated papillary thyroid carcinomas (PTC) being the most common variant, occurring in about 80–90% of all cases.The unique features of differentiated thyroid cancer (DTC) cells are: ability to take up iodine, presence of the thyroid-stimulating hormone (TSH) receptor, synthesis of thyroglobulin (Tg) and, in some cases, synthesis of thyroid hormones
In order to gain insight into possible cellular and molecular mechanisms underlying the stunning phenomenon, we performed a panel of experiments on cultured K1 cells exposed to various absorbed doses of 131 I in vitro

Summary

Introduction

The unique features of differentiated thyroid cancer (DTC) cells are: ability to take up iodine, presence of the thyroid-stimulating hormone (TSH) receptor, synthesis of thyroglobulin (Tg) and, in some cases, synthesis of thyroid hormones These characteristics of DTC enable the use of radioactive iodine, especially 131 I, in diagnostic and therapeutic procedures in this particular disease. Literature data indicate that administration of a radioisotope in a diagnostic dose may decrease further the radioiodine uptake—the phenomenon called “thyroid stunning” It was first described in 1951, and in the years provoked numerous attempts to confirm its existence and/or clarify the underlying molecular mechanisms [2,3,4,5,6,7,8,9,10,11,12,13,14]. 131 I uptake in malignant thyroid tissue is almost always much lower than that in normal thyroid tissue [16]

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