In vitro studies on the toxicity of isoniazid in different cell lines

The aim of the present study was to investigate in vitrothe mechanism of toxicity of isoniazid (-INH), the drug most widely used for treatment of tuberculosis. The human hepatoma line HepG2, the human lymphoblastoid line AHH-1 and the murine lymphoma cells YAC-1 were used as test systems. Active cell death (-apoptosis) and necrosis were detected by different flow cytometric methods: the binding of annexin V to the cell membrane and staining with propidium iodide (PI), the TUNEL assay for detection of DNA fragmentation and the occurrence of a sub G1 peak in cell cycle histograms. Mitochondrial membrane potential was analysed with the fluorescent probe JC-1. In addition to cytotoxicity, effects of INH on cell cycle were studied in HepG2 cells. The data of the present investigations indicate that INH induces cytotoxicity via apoptosis both in hepatoma and lymphoma cells. Twenty-four hours of application of INH in concentrations -26 mM led to a remarkable number of apoptotic cells positive for Annexin V. The ...