MARCIA AUGUSTA DA SILVA
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Artigo IPEN-doc 23214 Cytotoxic and genotoxic effects of I-131 and Co-60 in follicular thyroid cancer cell (WRO) with and without recombinant human thyroid-stimulating hormone treatment2017 - VALGODE, FLAVIA G.S.; SILVA, MARCIA A. da; VIEIRA, DANIEL P.; RIBELA, MARIA T.C.P.; BARTOLINI, PAOLO; OKAZAKI, KAYONormally, 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-131 and Co-60 and radioiodine uptake in WRO cells, derived from DTC, harboring the BRAF(V600E) 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-131 (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-60 (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-131, 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-131 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-131 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.Artigo IPEN-doc 08666 Induction of micronuclei by 153Sm-EDTMP in peripheral blood lymphocytes in vitro2002 - SUZUKI, M.F.; SILVA, M.A.; GUIMARAES, M.I.C.C.; OKAZAKI, K.The purpose of this study was to evaluate the degree of cytological radiation damage to lymphocytes induced by beta particle (71% E max = 810 keV) and gamma rays (29% E max = 103 keV) of 153Sm (T½ = 46.3 h). Samarium-153 ethylene diamine tetramethylene phosphonate (153Sm-EDTMP) has been successfully applied as a radiopharmaceutical for palliation of metastatic bone pain at dose of 37 MBq/kg (1mCi/kg) intravenously. Blood samples from four healthy donors and three patients with no previous radiotherapy were exposed to 370, 555 (equivalent to the activity administrated in vivo) and 1110 kBq/mL during one hour in vitro. Then the lymphocytes were cultured for cytokinesis block micronucleus assay that has received increased attention for biological monitoring of radiation exposure. The MN induction in binucleated cells (BNC) at 370 and 555 kBq/mL was not significantly increased and showed no difference between the groups. This result may be explained as a consequence of the sensibility of this technique. The radiation damage to peripheral blood lymphocytes (PBL) exposed to 1110 kBq/mL may be considered to be equivalent to that observed after an external irradiation with 60Co at doses of 0.38 Gy in healthy donors (MN/BNC = 0.053 ± 0.041) and 0.51 Gy in patients (MN/BNC = 0.069 ± 0.040). This study showed that the use of 153 Sm-EDTMP induced no significant increase in the micronucleation of PBL at radioactive concentration lower than 555 kBq/mL (37MBq/kg) and also that the radiosensitivity of the patients was higher at 1110 kBq/mL than that of the healthy donors.Artigo IPEN-doc 12287 Genotoxic evaluation of [DOTA, Tyrsup(3)]octreotate labelled with sup(131)I and sup(177)Lu in human peripheral lymphocytes in vitro by micronucleus assay2007 - SUZUKI, MIRIAM F.; SILVA, MARCIA A. da; CALDEIRA FILHO, JOSE de S.; COLTURATO, MARIA T.; ARAUJO, ELAINE B. de; BARTOLINI, PAOLO; OKAZAKI, KAYO[DOTA, Tyr3 ]octreotate has been used for cancer diagnosis and therapy because of its high affinity to somatostatin subtype receptors sstr2 and sstr5. The aim of this study was to evaluate the cytogenetic effect of radio-labelled [DOTA, Tyr3 ]octreotate in blood cells in vitro, using the cytokinesis-block micronucleus assay. Blood samples of healthy donors were exposed to different activities of [DOTA, Tyr3 ]octreotate labelled with 131I (n = 3) and 177Lu (n = 3), where radioactive concentration ranged from 600 to 5600 kBq/mL. The cells were cultivated according to criteria adopted by the IAEA (Vienna). The results showed a positive correlation between radioactive concentrations (X) and the frequency of binucleated cells with micronuclei (Y) (P < 0.05). The linear equations were similar: for the 131I labelled, Y = (1.634 ± 0.236) + (0.912 ± 0.137) 10–3 X and for the 177Lu labelled, Y = (1.715 ± 0.342) + (0.743 ± 0.135) 10–3 X.