RESUMEN
BACKGROUND: Early-stage breast cancer is usually treated with breast-conserving surgery followed by adjuvant radiation therapy. Acute skin toxicity is a common radiation-induced side effect experienced by many patients. Recently, a combination of bisphosphonates (zoledronic acid) and statins (pravastatin), or ZOPRA, was shown to radio-protect normal tissues by enhancing DNA double-strand breaks (DSB) repair mechanism. However, there are no studies assessing the effect of ZOPRA on cancerous cells. The purpose of this study is to characterize the in vitro effect of the zoledronic acid (ZO), pravastatin (PRA), and ZOPRA treatment on the molecular and cellular radiosensitivity of breast cancer cell lines. MATERIALS: Two breast cancer cell lines, MDA MB 231 and MCF-7, were tested. Cells were treated with different concentrations of pravastatin (PRA), zoledronate (ZO), as well as their ZOPRA combination, before irradiation. Anti-γH2AX and anti-pATM immunofluorescence were performed to study DNA DSB repair kinetics. MTT assay was performed to assess cell proliferation and viability, and flow cytometry was performed to analyze the effect of the drugs on the cell cycle distribution. The clonogenic assay was used to assess cell survival. RESULTS: ZO, PRA, and ZOPRA treatments were shown to increase the residual number of γH2AX foci for both cell lines. ZOPRA treatment was also shown to reduce the activity of the ATM kinase in MCF-7. ZOPRA induced a significant decrease in cell survival for both cell lines. CONCLUSIONS: Our findings show that pretreatment with ZOPRA can decrease the radioresistance of breast cancer cells at the molecular and cellular levels. The fact that ZOPRA was previously shown to radioprotect normal tissues, makes it a good candidate to become a therapeutic window-widening drug.
Asunto(s)
Neoplasias de la Mama , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Femenino , Células MCF-7 , Reparación del ADN , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Difosfonatos/farmacología , Ácido Zoledrónico/farmacología , Pravastatina/farmacología , Tolerancia a Radiación/efectos de la radiación , ADN , Línea Celular TumoralRESUMEN
ABSTRACT Several molecules and events involved in cell response to radiation-induced damage have been investigated towards a personalized radiotherapy. Considering the importance of active caspase-3 in the proteolytic cascade that ensures radiation-induced apoptosis execution, this research was designed to evaluate the expression levels of this protein as a bioindicator of individual radiosensitivity. Peripheral blood samples of 10 healthy individuals were gamma-irradiated (cobalt-60 source) with 1, 2 and 4 Gy (control: non-irradiated samples), and active caspase-3 expression levels were measured in lymphocytes, by flow cytometry, ex vivo and after different times of in vitro incubation (24, 48 and 72 hours). Short-term incubation of 24 h was the most adequate condition to evidence correlations between dose radiation and active caspase-3 expression. For each radiation dose, it was observed a significant inter-individual variation in active caspase-3 expression intensity, suggesting that this parameter may be suitable for evidence individual radiosensitivity. The methodology presented and discussed in this work may help to predict healthy tissues response to radiation exposure toward the better patient outcome.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Tolerancia a Radiación/efectos de la radiación , Linfocitos/efectos de la radiación , Radioisótopos de Cobalto , Apoptosis/efectos de la radiación , Caspasa 3/metabolismo , Linfocitos/enzimología , Biomarcadores Ambientales , Relación Dosis-Respuesta en la Radiación , Citometría de FlujoRESUMEN
OBJECTIVE: To investigate the effect of elemene on the radiosensitivity of A549 cells and its possible molecular mechanism. METHODS: Apoptosis of A549 cells was detected by flow cytometry and fluorescence microscopy. The effect of double-strand break (DSB) damage repair in A549 cells was evaluated using the neutral comet assay. Protein expression levels were detected using western blotting, and the correlation between protein levels was analyzed. RESULTS: Elemene exhibited a radiosensitizing effect on A549 cells. The level of apoptosis induced by elemene combined with radiation was significantly greater (p<0.01) than that elicited by either radiation or elemene alone. Following radiation and subsequent repair for 24 h, the tail intensity of A549 cells treated with a combination of elemene and radiation was greater than that of cells treated with either elemene or radiation alone (p<0.01). This result indicates that elemene inhibits cellular DSB repair. Both elemene combined with radiation and radiation alone decreased the protein expression of DNA-PKcs and Bcl-2 compared to elemene alone (p<0.01), while p53 protein expression was increased (p<0.01). A negative correlation was observed between DNA-PKcs and p53 expression (r=−0.569, p=0.040), while a positive correlation was found between DNA-PKcs and Bcl-2 expression (r=0.755, p=0.012). CONCLUSIONS: Elemene exhibits a radiosensitizing effect on A549 cells, and its underlying molecular mechanism of action may be related to the downregulation of DNA-PKcs gene expression. .
Asunto(s)
Humanos , Adenocarcinoma/radioterapia , Neoplasias Pulmonares/radioterapia , Tolerancia a Radiación/efectos de la radiación , Fármacos Sensibilizantes a Radiaciones/farmacología , Sesquiterpenos/farmacología , Análisis de Varianza , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Western Blotting , Línea Celular Tumoral , Ensayo Cometa , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Reparación del ADN/efectos de los fármacos , Reparación del ADN/efectos de la radiación , Proteína Quinasa Activada por ADN/metabolismo , Citometría de Flujo , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de la radiación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Microscopía Fluorescente , Dosis de Radiación , Tolerancia a Radiación/efectos de los fármacos , /metabolismoRESUMEN
FUNDAMENTOS: Existe um consenso de que a exposição à radiação ultravioleta determina alterações n o sistema imunológico da pele, o que permite que se avente a hipótese de que a exposição prolongada e crônica ao Sol pode representar uma das maiores agressões ambientais à saúde humana. Entre as várias ocupações que requerem, necessariamente, exposição prolongada e crônica ao Sol está a de pescador. No entanto, a experiência clínica dermatológica, amealhada ao longo de vários anos de exercício da Medicina, não parece confirmar essa hipótese. OBJETIVO: Avaliar efeitos clínicos, histológicos e imunológicos da exposição crônica e prolongada à radiação ultravioleta em pescadores. MÉTODOS: Em estudo prospectivo, transversal, observacional, foram caracterizadas lesões dermatológicas, marcadores imunológicos e alterações histológicas de pescadores e subpopulações de linfócitos comparadas a grupo-controle. Empregaram-se testes de Mann-Whitney, exato de Fisher, Wilcoxon em nível de 0,05. RESULTADOS: Houve diferenças entre os grupos exposto e protegido em elastose (p = 0,03), ectasia de vasos dérmicos (p = 0,012) e número de células nas camadas epidérmicas entre os cones (p = 0,029). Foram mais comuns em pescadores CD45RO, CD68+ e mastócitos na pele (p = 0,040, p < 0,001 e p = 0,001); CD3CD8CD45RO no sangue (p = 0,016). CONCLUSÃO: As alterações sugerem que exposição crônica e prolongada ao sol promove tolerância à radiação ultravioleta, protetora da imunossupressão.
BACKGROUND: Among the various occupations which necessarily require long-term and chronic sun exposure is that of a fisherman. However, clinical experience in dermatology earned over several years of medical practice does not seem to confirm this hypothesis. OBJECTIVE: To evaluate clinical, histological and immunological effects of long-term and chronic exposure to ultraviolet radiation in fishermen. METHODS: A prospective, cross-sectional and observational study characterized skin lesions, immunological markers and histological alterations in fishermen, as well as lymphocyte subpopulations compared to a control group. Mann-Whitney, Fisher's and Wilcoxon statistical tests were used at a significance level of 0.05. RESULTS: There were significant differences between the exposed group and the group protected due to elastosis (p = 0.03), ectasia of dermal vessels (p = 0.012) and number of cells in the epidermal layers between cones (p = 0.029). Most common among fishermen were CD45RO, CD68 + and mastocytes in the skin (p = 0.040, p <0.001, p = 0.001) and CD3CD8CD45RO in the blood (p = 0.016). CONCLUSION: The alterations suggest that long-term and chronic sun exposure promotes tolerance to ultraviolet radiation, which protects against immunosuppression.
Asunto(s)
Adulto , Humanos , Masculino , Persona de Mediana Edad , Exposición a Riesgos Ambientales/efectos adversos , Explotaciones Pesqueras , Conocimientos, Actitudes y Práctica en Salud , Piel/efectos de la radiación , Luz Solar/efectos adversos , Rayos Ultravioleta/efectos adversos , Brasil , Estudios de Casos y Controles , Estudios Transversales , Linfocitos/citología , Linfocitos/efectos de la radiación , Enfermedades Profesionales/inmunología , Estudios Prospectivos , Tolerancia a Radiación/inmunología , Tolerancia a Radiación/efectos de la radiación , Piel/inmunologíaRESUMEN
Gestantes podem precisar ser submetidas a exames radiológicos para um diagnóstico preciso e conduta correta. Nestes casos a exposição à radiação ionizante e seus efeitos sobre o feto são motivo de preocupação para a paciente e o seu médico. Na verdade, a maioria destes exames é segura e não oferece risco significativo ao feto. No entanto, é importante que o radiologista conheça estes riscos potenciais para poder orientar adequadamente todos os envolvidos no atendimento.
X-ray examinations may be necessary during pregnancy for an accurate diagnosis and adequate treatment administration. In these cases, the exposure to ionizing radiation and its effects on the fetus are a major concern to the patient and to the clinician. In fact, most of these examinations are safe and do not represent a significant risk to the fetus. However, the radiologist must know the potential risks to be able to instruct all personnel involved in the care of the patient.
Asunto(s)
Humanos , Femenino , Embarazo , Embarazo/efectos de la radiación , Radiación , Exposición a la Radiación , Diagnóstico por Imagen/efectos adversos , Dosis de Radiación , Radiación Ionizante , Tolerancia a Radiación/efectos de la radiaciónAsunto(s)
Alimentos Congelados/efectos de la radiación , Enfermedades Transmisibles , Contaminación de Alimentos/prevención & control , Enfermedades Transmitidas por los Alimentos , Radiación Ionizante , Mariscos , Smegmamorpha , Tolerancia a Radiación/efectos de la radiación , Trematodos/efectos de la radiación , Peces , Parasitología de Alimentos , Congelación , Salud PúblicaRESUMEN
A irradiação é considerada um dos processos tecnológicos mais eficientes na redução de microrganismos patogênicos e deteriorantes dos alimentos. As ostras são moluscos bivalves que, frequentemente, são consumidas cruas, sendo consideradas importantes veículos de microrganismos patogênicos, devido à sua capacidade de filtração. O objetivo deste estudo foi avaliar a radiossensibilidade de Salmonella spp e Vibrio parahaemolyticus incorporadas artificialmente por ostras (Crassostrea brasiliana). As ostras foram submetidas ao tratamento de radiação gama com doses variando entre 0,5 kGy a 3,0 kGy. Os valores de D10 variaram de 0,44 kGy a 0,55 kGy para Salmonella spp e de 0,15 kGy a 0,19 kGy para Vibrio parahaemolyticus...