MARCIA AUGUSTA DA SILVA

MARCIA AUGUSTA DA SILVA

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Cytotoxic and genotoxic effects of I-131 and Co-60 in follicular thyroid cancer cell (WRO) with and without recombinant human thyroid-stimulating hormone treatment
2017 - VALGODE, FLAVIA G.S.; SILVA, MARCIA A. da; VIEIRA, DANIEL P.; RIBELA, MARIA T.C.P.; BARTOLINI, PAOLO; OKAZAKI, KAYO
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-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.
Cytotogenic and dosimetric effects of sup(131)I in patients with differentiated thyroid carcinoma: comparison between stimulation with rhTSH and thyroid hormone withdrawal treatments
2016 - SILVA, MARCIA A. da; VALGODE, FLAVIA G.S.; GONZALEZ, JULIA A.; YORIYAZ, HELIO; GUIMARAES, MARIA I.C.C.; RIBELA, MARIA T.C.P.; BUCHPIGUEL, CARLOS A.; BARTOLINI, PAOLO; OKAZAKI, KAYO
A study directed to the cytogenetic and dosimetric aspects of radionuclides of medical interest is very valuable, both for an accurate evaluation of the dose received by the patients, and consequently of the genetic damage, and for the optimization of therapeutic strategies. Cytogenetic and dosimetric effects of 131I in lymphocytes of thyroidectomized differentiated thyroid cancer (DTC) patients were evaluated through chromosome aberration (CA) technique: Euthyroid patients submitted to recombinant human thyroid-stimulating hormone (rhTSH) therapy (group A) were compared with hypothyroid patients left without levothyroxine treatment (group B). CA analysis was carried out prior to and 24 h, 1 week, 1 month and 1 year after radioiodine administration (4995–7030 MBq) in both groups. An activity–response curve of 131I (0.074–0.740 MBq/mL) was elaborated, comparing dicentric chromosomes in vivo and in vitro in order to estimate the absorbed dose through Monte Carlo simulations. In general, radioiodine therapy induced a higher total CA rate in hypothyroid patients as compared to euthyroid patients. The frequencies of dicentrics obtained in DTC patients 24 h after treatment were equivalent to those induced in vitro (0.2903 ± 0.1005 MBq/mL in group A and 0.2391 ± 0.1019 MBq/mL in group B), corresponding to absorbed doses of 0.65 ± 0.23 Gy and 0.53 ± 0.23 Gy, respectively. The effect on lymphocytes of internal radiation induced by 131I therapy is minimal when based on the frequencies of CA 1 year after the treatment, maintaining a higher quality of life for DTC patients receiving rhTSHaided therapy.
Comparison of the cytogenetic effects of sup(131)I in patients with differentiated thyroid cancer with and without prior treatment with rhtsh
2013 - VALGODE, FLAVIA G.S.; SILVA, MARCIA A. da; GONZALEZ, JULIA A.; YORIYAZ, HELIO; GUIMARAES, MARIA I.C.C.; RIBELA, MARIA T. de C.P.; BUCHPIGUEL, CARLOS A.; BARTOLINI, PAOLO; OKAZAKI, KAYO
Induction of chromosomal aberrations in human lymphocytes by fission neutrons
2009 - SILVA, MARCIA A.; COELHO, PAULO R.P.; BARTOLINI, PAOLO; OKAZAKI, KAYO
Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients
2001 - NASCIMENTO, P.A.; SILVA, M.A.; OLIVEIRA, E.M.; SUZUKI, M.F.; OKAZAKI, K.
Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the dose-response curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.
Evaluation of the effect of 90Sr β-radiation on human blood cells by chromosome aberration and single cell gel electrophoresis (comet assay) analysis
2001 - OLIVEIRA, E.M.; SUZUKI, M.F.; NASCIMENTO, P.A.; SILVA, M.A.; OKAZAKI, K.
Among various environmental genotoxins, ionizing radiation has received special attention because of its mutagenic, carcinogenic and teratogenic potential. In this context and considering the scarcity of literature data, the objective of the present study was to evaluate the effect of 90Sr β-radiation on human cells. Blood cells from five healthy donors were irradiated in vitro with doses of 0.2-5.0 Gy from a 90Sr source (0.2 Gy/min) and processed for chromosome aberration analysis and for comet assay. The cytogenetic results showed that the most frequently found aberration types were acentric fragments, double minutes and dicentrics. The α and β coefficients of the linear-quadratic model, that best fitted the data obtained, showed that 90Sr β-radiation was less efficient in inducing chromosome aberrations than other types of low linear energy transfer (LET) radiation such as 3H β-particles, 60Co γ-rays, 137Cs and 192Ir and X-rays. Apparently, 90Sr β-radiation in the dose range investigated had no effect on the modal chromosome number of irradiated cells or on cell cycle kinetics. Concerning the comet assay, there was an increase in DNA migration as a function of radiation dose as evaluated by an image analysis system (tail moment) or by visual classification (DNA damage). The dose-response relation adequately fitted the non-linear regression model. In contrast to the cytogenetic data, 90Sr β-radiation induced more DNA damage than 60Co γ-radiation when the material was analyzed immediately after exposures. A possible influence of selective death of cells damaged by radiation was suggested.
Induction of micronuclei by 153Sm-EDTMP in peripheral blood lymphocytes in vitro
2002 - 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.
Genotoxic evaluation of [DOTA, Tyrsup(3)]octreotate labelled with sup(131)I and sup(177)Lu in human peripheral lymphocytes in vitro by micronucleus assay
2007 - 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.
Evaluation of the cytogenetic effects of 131I preceded by recombinant human thyrotropin (rhTSH) in peripheral lymphocytes of Wistar rats
2008 - SILVA, MARCIA A. da; GUIMARAES, MARIA I.C.C.; YORIYAZ, HELIO; RIBELA, MARIA T.C.P.; BUCHPIGUEL, CARLOS A.; BARTOLINI, PAOLO; OKAZAKI, KAYO
The present study was carried out to investigate the cytogenetic effects of therapeutic exposure to radioiodine preceded by rhTSH in an animal model. Three groups of Wistar rats (n = 6) were used: one group was treated only with 131I (11.1 MBq/animal); the other two groups received rhTSH (1.2 μg/rat of either Thyrogen or rhTSH-IPEN, respectively) 24 h before administration of radioiodine. The percentage of lymphocytes with chromosome aberrations and the average number of aberrations and of dicentrics per cell were determined on blood samples collected 24 h, 7 and 30 days after administration of 131I. The data show that the treatment with radioiodine alone or associated with rhTSH resulted in a greater quantity of chromosome alterations in relation to basal values after 24 h, with a gradual decline after 7 and 30 days of treatment. An increase in chromosome alterations was also seen after rhTSH treatment alone. Neither of the treatments, i.e., with 131I alone or associated with hormone, resulted in an aneugenic effect or influenced the kinetics of cellular proliferation in rat blood lymphocytes. There was no significant difference between the cytogenetic effects of Thyrogen and rhTSH-IPEN treatment. These data suggest that the treatment with radioiodine, associated or not with rhTSH, affects to a limited extent a relatively small number of cells although the occurrence of late stochastic effects could not be discarded.