Radioiodide induces apoptosis in human thyroid tissue in culture

Abstract

Radioiodide ((131)I) is routinely used for the treatment of toxic adenoma, Graves' disease, and for ablation of thyroid remnant after thyroidectomy in patients with thyroid cancer. The toxic effects of ionizing radiations on living cells can be mediated by a necrotic and/or apoptotic process. The involvement of apoptosis in radiation-induced cell death in the thyrocytes has been questioned. The knowledge of the mechanisms that underlie the thyrocyte death in response to radiations can help to achieve a successful treatment with the lowest (131)I dose. We developed a method to study the effects of (131)I in human thyroid tissue in culture, by which we demonstrated that (131)I induces thyroid cell apoptosis. Human thyroid tissues of about 1 mm(3) were cultured in vitro and cell viability was determined up to 3 weeks by the MTT assay. Radioiodide added to the culture medium was actively taken up by the tissues. The occurrence of apoptosis in the thyrocytes was assessed by measuring the production of a caspase-cleavage fragment of cytokeratin 18 (M30) by an enzyme-linked immunoassay. Neither variation of cell number nor spontaneous apoptosis was revealed after 1 week of culture. (131)I added to the culture medium induced a dose-dependent and a time-dependent generation of M30 fragment. The apoptotic process was confirmed by the generation of caspase-3 and PARP cleavage products. These results demonstrate that (131)I induces apoptosis in human thyrocytes. Human thyroid tissue cultures may be useful to investigate the cell death pathways induced by (131)I.

Radiation and Thyroid Cancer

“…During the cell proliferation phase, the cell cycle was shortened by approximately 50%, predominantly due to a decrease of the G1-phase duration [24]. 131 I was shown to trigger apoptosis in human thyrocytes [25]. The cell viability of human thyroid epithelial cells purified from surgical tissue specimens was not affected by single doses of 5 or 50 Gy IR, and there was no induction of Heat shock proteins (HSP)-72, as an indicator of acute cellular stress.…”

“…Synopsis of the main literature in the field [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45]. HLA-DR: human leukocyte antigen-DR; RET/PTC : rearranged during transfection/papillary thyroid carcinoma; PKC: protein kinase C; MAPKK7: mitogen-activated protein kinase 7; JNK: c-Jun NH2-terminal kinases; IR: ionizing radiation; UV: ultraviolet rays; ROS: reactive oxygen species.…”

Challenges and current views on dosing of radioactive iodine in the treatment of benign thyroid disease

“…Direktni efekti podrazumijevaju direktna oštećenja DNK i drugih makromolekula dejstvom beta čestica, dok indirektni efekti uključuju stvaranje slobodnih radikala, koji zatim reaguju sa makromolekulama (4,6). Procesi apoptoze i/ili nekroze, inicirani oštećenjima u tireocitima (11,12), dovode do smanjenja funkcije, odnosno veličine štitaste žlijezde, tj. omogućavaju postizanje terapijskog cilja (6).…”

“…SI jedinica za dozu apsorbovanog zračenja je Gray (1 J/kg = 1 Gy). Generalno, što je veća doza apsorbovanog zračenja, niža je frakcija ćelija koje prežive zračenje, mada je odnos doza-efekat veoma složen i uključuje ćelijske mehanizme adaptacije (6,12).…”

Moving toward a better understanding of radioiodine action

“…In this issue of endocrine, Russo et al [1] evaluate the mechanism of 131 I-mediated cytotoxicity. The investigators approached this question by developing a method for culturing small thyroid tissues for up to 3 weeks in vitro.…”