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Cytotoxic and genotoxic effects of 131I and 60Co in follicular thyroid cancer cell (WRO) with and without recombinant human thyroid‐stimulating hormone treatment
Authors:Flávia Gomes Silva Valgôde  Márcia Augusta da Silva  Daniel Perez Vieira  Maria Teresa Carvalho Pinto Ribela  Paolo Bartolini  Kayo Okazaki
Affiliation:Centro de Biotecnologia, Instituto de Pesquisas Energéticas e Nucleares, IPEN‐CNEN/SP, S?o Paulo, Brazil
Abstract:Normally, differentiated thyroid cancer (DTC) tends to be biologically indolent, highly curable and has an excellent prognosis. However, the treatment may fail when the cancer has lost radioiodine avidity. The present study was carried out in order to evaluate the cytotoxic and genotoxic effects of 131I and 60Co and radioiodine uptake in WRO cells, derived from DTC, harboring the BRAFV600E mutation. WRO cells showed a relatively slow cell cycle of 96.3 h with an unstable karyotype containing various double minutes. The genotoxicity assay (micronucleus test) showed a relative high radioresistance to 131I (0.07–3.70 MBq/mL), independent of treatment with recombinant human thyroid‐stimulating hormone (rhTSH). For the cytotoxicity assay, WRO cells were also relatively resistant to 60Co (range: 0.2–8.3 Gy), but with a gradual decrease of viability as a function of time for higher doses (20 and 40 Gy, starting from the fifth to sixth day). For internal irradiation with 131I, WRO cells showed a decline in viability at radioactive concentration higher than 1.85 MBq/mL; this was even more effective at 3.70 MBq/mL, but only when preceded by rhTSH, in coincidence with the highest level of 131I uptake. These data show promising results, since the loss of the ability of thyroid cells to concentrate radioiodine is considered to be one of the main factors responsible for the failure of 131I therapy in patients with DTC. The use of tumor‐derived cell lines as a model for in vivo tumor requires, however, further investigations and deep evaluation of the corresponding in vivo effects. Environ. Mol. Mutagen. 58:451–461, 2017. © 2017 Wiley Periodicals, Inc.
Keywords:WRO cell  differentiated thyroid cancer  131I therapy  rhTSH  radioiodine uptake
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