Cytotoxic and genotoxic effects of 131 I and 60 Co in follicular thyroid cancer cell (WRO) with and without recombinant human thyroid-stimulating hormone treatment

• Published in: Environmental and molecular mutagenesis 2017-07, Vol.58 (6), p.451-461
• Main Authors: Valgôde, Flávia Gomes Silva, da Silva, Márcia Augusta, Vieira, Daniel Perez, Ribela, Maria Teresa Carvalho Pinto, Bartolini, Paolo, Okazaki, Kayo
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Follicular - drug therapy; Adenocarcinoma, Follicular - radiotherapy; Cell Count; Cell Death - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cobalt Radioisotopes - therapeutic use; Dose-Response Relationship, Radiation; Humans; Iodine Radioisotopes - therapeutic use; Metaphase - drug effects; Mutagens - toxicity; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Thyrotropin - pharmacology; Thyrotropin - therapeutic use
• ISSN: 0893-6692; 1098-2280
• DOI: 10.1002/em.22099

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 I and Co and radioiodine uptake in WRO cells, derived from DTC, harboring the BRAF 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 I (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 Co (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 I, 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 I 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 I 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.