PARTICIPATION OF BAX-ALPHA IN IFN-ALPHA-MEDIATED APOPTOSIS IN DAUDI B-LYMPHOMA-CELLS

Although interferon-alpha (IFN-alpha) has proved beneficial in the tre atment of some tumors, the basis for this is still uncertain. In this study, we examined the effects of IFN-alpha on the growth of tumor cel ls in vitro, using the Daudi line of B lymphoma cells as a model, Ther e was a dose-dependent accumulation of these cells in the G(1) phase o f the cell cycle 24-48 h from the time of exposure to IFN-alpha. This was followed between 48 h and 96 h by an increasing degree of apoptosi s, as assessed by cell survival, propidium iodine staining, and transm ission electron microscopy. Concomitantly with the apoptosis, there wa s the appearance of p18 Bax-alpha, an apparently novel variant low mol ecular weight form of the p21 Bax-alpha found in normal cells. There w as also a slight diminution in Bcl-x(L), with a resultant drop in the Bcl-x(L):Bax-alpha ratio, Treatment of cells with CD40-L partially inh ibited the development of apoptosis in response to IFN-alpha. At the s ame time, generation of p18 Bax-alpha was reduced, which suggests that this plays a part in the apoptotic process. These findings may throw light on the development of lymphomas and perhaps point to future ways of improving therapy with IFN-alpha.