RESUMEN
BACKGROUND: Proteins overexpressed in malignant tissues form important targets in the development of targeted therapeutics, and aptamers comprise an important affinity agent for therapy and drug delivery. In this study, aberrantly expressed mucin 1 glycoprotein was investigated as a therapeutic target in a breast cancer model. MATERIALS AND METHODS: In order to determine the feasibility of using an aptamer against mucin 1 (aptA) as carrier of the cytotoxic compound 1,10-phenanthroline to MCF-7 cells, as a potential radiosensitizer, was studied in experiments using circular dichroism and rhodamine labelling by fluorescent microscopy and flow cytometry. RESULTS: 1,10-Phenanthroline can be intercalated within aptA when complexed with Fe(II) ions, with dissociation constant (Kd) of 30 µM. The complex was subsequently capable of binding to and being internalised in MCF-7 breast cancer cells. CONCLUSION: aptA can carry 1,10-phenanthroline to cancer cells specifically and this complex represents a potential target-directed anticancer therapy.
Asunto(s)
Aptámeros de Nucleótidos/metabolismo , Neoplasias de la Mama/metabolismo , Portadores de Fármacos , Endocitosis , Mucina-1/metabolismo , Fenantrolinas/metabolismo , Fármacos Sensibilizantes a Radiaciones/metabolismo , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Estudios de Factibilidad , Femenino , Compuestos Ferrosos/química , Humanos , Células MCF-7 , Mucina-1/genética , Fenantrolinas/química , Fenantrolinas/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacologíaRESUMEN
Lanthanum (La) is a rare-earth metal with applications in agriculture, industry, and medicine. Since lanthanides show a broad spectrum of applications there is an increased risk of contamination for humans. We examined the effects of lanthanum in Jurkat cells and human peripheral lymphocytes (HPL), and we found that it was cytotoxic and genotoxic on both cell lines. Additionally, HPL were more sensitive to La treatment than Jurkat cells and necrosis was the pathway by which La induced cytotoxicity. Vitamin E was able to diminish the DNA strand breaks induced suggesting that oxidative stress may be involved in the genotoxic process.
Asunto(s)
Carcinógenos/toxicidad , Contaminantes Ambientales/toxicidad , Lantano/toxicidad , Linfocitos/efectos de los fármacos , Mutágenos/toxicidad , Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Antagonismo de Drogas , Combinación de Medicamentos , Contaminantes Ambientales/clasificación , Humanos , Células Jurkat , Lantano/clasificación , Linfocitos/patología , Necrosis/inducido químicamente , Vitamina E/farmacologíaRESUMEN
Twenty ropes with 400 Perna perna mussels seeds (3 cm shell size) were set-up on floating structures at Cabo Frio Island, Arraial do Cabo, approximately 100 km northeast of Rio de Janeiro city. A rope was taken out on a monthly basis, and the shell sizes of 100 seeds were measured. The haemolymph of 10 male and 10 female individuals was taken, and the same individuals were separated for 210Po/210Pb determination. After one year of monthly sampling, no clear correlation was observed between the 210Po concentration, mussel's age and weight. A mean 210Po concentration of 155 Bq kg(-1) wet weight basis, was obtained, which is comparable with data reported in the literature. The radiation dose did not have any observable effect on the micronuclei frequency and DNA breaks in the mussels. This was probably due to the low dose rate, 0.02 mGy d(-1), in comparison with the suggested potential dose limit of 10 mGy d(-1).