MARCIA AUGUSTA DA SILVA

MARCIA AUGUSTA DA SILVA

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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.
Análise citogenética do 153Sm-EDTMP em linfócitos periféricos de pacientes com câncer ósseo metastático
2002 - SILVA, M.A.; SUZUKI, M.F.; GUIMARAES, M.I.C.C.; BUCHPIGUEL, C.A.; ROGERO, J.R.; OKAZAKI, K.
O 153Sm-EDTMP é um radiofármaco utilizado em medicina nuclear com resultados promissores no alívio da dor metastática. No entanto, pouco se sabe sobre os efeitos do 153Sm-EDTMP em nível celular. O presente trabalho foi conduzido com o intuito de avaliar os efeitos citogenéticos do 153Sm-EDTMP em linfócitos periféricos de pacientes com metástases ósseas (com e sem radio e/ou quimioterapias anteriores) pela técnica de aberrações cromossômicas. Para tanto, as amostras sangüíneas foram coletadas antes e 1 hora após a administração endovenosa do 153Sm-EDTMP (atividade média de 42.53 ± 5.31 MBq/kg de peso corpóreo), levando-se em consideração o rápido clearance sangüíneo. Os tipos de aberrações cromossômicas estruturais mais freqüentes foram os double minutes e dicêntricos. A análise estatística mostrou que o único grupo de pacientes que apresentou uma diferença significativa na freqüência de aberrações cromossômicas 1 hora após o tratamento foi o que recebeu prévio tratamento radio e quimioterápico antes da terapia com 153Sm-EDTMP. Quanto a averiguação do número modal de cromossomos e da cinética do ciclo celular, a análise estatística mostrou que não houve diferença significativa entre os grupos analisados, sugerindo que o tratamento com 153Sm-EDTMP não influenciou nesses parâmetros. Os dados obtidos mostraram que a terapia com 153Sm-EDTMP induziu uma pequena quantidade de danos citogenéticos em linfócitos periféricos de pacientes 1 hora após a sua administração, embora, teoricamente, um efeito estocástico a longo prazo não possa ser descartado.
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.