ABSTRACT
PURPOSE: We hypothesize that the cytolytic activity of Bacillus Calmette-Guerin (BCG) may act through nitric oxide (NO) production, and that cell death is correlated with apoptosis, changes of NO and cell proliferation following BCG and/or nitric oxide synthase (NOS) inhibition treatment of a murine bladder tumor-2 (MBT-2) cell line. If these cell lines show cell death due to apoptosis was also determined. MATERIALS AND METHODS: NO production and proliferation activity of the MBT-2 cell line were measured after stimulation, with BCG and/or L-NAME, using an enzyme- linked immunosorbent assay (ELISA). After incubation of the MBT-2 cells with BCG and/or L-NAME, the cell cycle was analysis was performed by immunocytometry. RESULTS: The production of NO in the MBT-2 cells was significantly increased by the BCG. The BCG had direct dose-dependent cytotoxic effects on the MBT-2 cell line. After the L-NAME treatment, both the NO production and cytotoxicity were decreased (p<0.05). When the MBT-2 cells were cultured with BCG, the apoptotic cell ratio increased compared to that of the MBT-2 cells treated with L-NAME (p<0.05). CONCLUSIONS: The up-regulation of the production of NO following BCG treatment of the MBT-2 cell line may be due, in part, to the cytolytic action of the BCG. The cell death, when BCG was instilled, correlated with apoptosis.