REGULATION OF CELL-SURVIVAL IN BURKITT-LYMPHOMA - IMPLICATIONS FROM STUDIES OF APOPTOSIS FOLLOWING COLD-SHOCK TREATMENT

Burkitt lymphoma (BL) tumour-cell populations are known to display high rates both of proliferation and of apoptosis in vivo, but the mechanisms which determine whether a BL cell continues to cycle or engages its cell-death programme are not understood. Group-I BL-derived cell lines, which retain in vitro the proliferative and apoptotic capacities of the parental cells, selectively entered apoptosis when returned to 37 degrees C after a brief period at low temperature (1 degrees C). The induction of apoptosis by cold treatment, as determined by morphological characteristics and DNA fragmentation, was readily detectable within the first 1 to 2 hr of re-incubation at 37 degrees C, reaching a maximum at 4 to 6 hours. Commitment to enter apoptosis occurred after as little as 20 to 30 min at 1 degrees C. Significant cell death at 1 degrees C occurred only during prolonged incubation in the cold and displayed the characteristics of necrosis. Both bcl-2-dependent and -independent survival pathways were found to provide protection from cold-induced apoptosis, but only if engaged before cold-shock treatment. These results indicate that continued cycling of group-1 BL cells is dependent upon their capacity to inhibit or circumvent their normally constitutively active apoptotic programme, and are consistent with the notion that the synthesis of one or more critical ''survival'' proteins of short half-life is necessary to guarantee successful passage through the cell cycle. Notably, high levels of apoptosis were also inducible in group-1 BL cells by inhibitors of RNA and protein synthesis. (C) 1994 Wiley-Liss, Inc.