RESUMO
The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR) enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1) transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or loss.
Assuntos
Animais , Camundongos , Adipócitos/efeitos dos fármacos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aziridinas/farmacologia , Proteínas de Escherichia coli/genética , Genes Transgênicos Suicidas/efeitos dos fármacos , Técnicas de Cultura de Células , Diferenciação Celular , Estudos de Viabilidade , Fatores de Tempo , Transfecção/métodosRESUMO
Se estudiaron cuatros operarios sobre un total de diez afectados, que trabajaban en una empresa de productos farmacéuticos para veterinaria que manipulaban etilenimina para la elaboración de vacuna antiaftosa. El objeto del presente trabajo fue determinar si la E. es el agente causal en diez operarios afectados por dermitis por contacto alérgica en una industria que la emplea y, en caso de confirmar esta participación, indicar las medidas de profilaxis respectiva
