MERCURIC CHLORIDE-INDUCED PROGRAMMED CELL-DEATH OF A MURINE T-CELL HYBRIDOMA .1. EFFECT OF THE PROTOONCOGENE BCL-2

Mercuric chloride (HgCl2) as well as several drugs can induce T cell a ctivation leading to systemic immune-mediated diseases in genetically susceptible individuals or rodents. T cell hybridomas represent a well -characterized model system for in vivo mechanisms of various stimuli- induced cell death. The cellular response to HgCl2 was examined using various T cell lines and particularly the murine T cell hybridoma 2B4. 11. Exposure to HgCl2 induced both necrosis and apoptosis in a dose- a nd time-dependent way as demonstrated by DNA fragmentation analysis, f low cytometry of the whole cells and of isolated nuclei, and morpholog ical examination. HgCl2-induced cell death was partly inhibited by cyc loheximide. The expression of human Bcl-2 in 2B4.11 cells after transf ection significantly prevented HgCl2-induced cell death but did not af fect the susceptibility to apoptosis induced by an anti-CD3 epsilon mA b. Subcytotoxic doses of HgCl2 enhanced metabolic activity of Bcl-2 tr ansfectants in contrast with mock-transfected cell line. Thus, we conc lude that apoptosis is part of the cell death process induced by HgCl2 and that the ability of Bcl-2 to prevent the death of one particular cell line is stimulus-dependent suggesting the existence of different pathways leading to cell death. (C) 1995 Academic Press, Inc.