RESUMEN
The herpes simplex virus thymidine kinase gene (HSV-tk) was stably transfected into rat C6 glioma cells (C6tk) in order to characterize the mechanisms underlying cell toxicity induced in vitro by the guanosine analog ganciclovir (GCV). The results demonstrate the efficiency of the HSV-tk/GCV system in ablating most of the tumoral cells within 7 to 8 days of treatment with 20 mivroM GCV; however, a few cells still survive. C6tk cells arrest in the S phase of the cell cycle after 2 days of drug treatment before undergoing cell death. Microscopic analysis reveals dying cells with ultrastructural characteristics consistent with apoptosis; we cannot rule out, however, that necrotic cell death may also be occurring. The cytotoxicity induced by GCV is not associated with changes in the expression of p53 protein, suggesting that cell cycle arrest and cell death may occur through a p53-independent pathway. C6tk cells constitutively express Bcl-xL and Bax proteins; when exposed to GCV, Bcl-xL levels do not change but Bax accumulation is rapidly induced. These findings suggest that the balance between Bcl-xL and Bax proteins may be of importance in determining the sensitivity of tumoral cells to GCV.
Asunto(s)
Muerte Celular/efectos de los fármacos , Ganciclovir/farmacología , Glioma/genética , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas/genética , Simplexvirus/enzimología , Timidina Quinasa/genética , Animales , Antivirales/farmacología , Muerte Celular/genética , División Celular/efectos de los fármacos , Glioma/enzimología , Glioma/patología , Ratas , Transfección , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Proteína X Asociada a bcl-2RESUMEN
The occurrence of filamentous bacteria was investigated in 15 French pulp and paper activated sludge wastewater treatment plant (WWTP). Large filamentous populations were present in most of the plants. Identification carried out with conventional methods based on morphological features and staining techniques showed that the four main filamentous bacteria encountered in these industrial WWTP and responsible for bulking belong to the genera Thiothrix sp., Type 021 N, Haliscomenobacter hydrossis and Type 0092. During two years a specific survey was performed for three of these WWTP showing recurrent bulking phenomena. Data from WWTP performance, chemical data and filaments characterization were compared to correlate the presence of specific filaments with process operating conditions.