INTERLEUKIN-3 END BCL-2 COOPERATIVELY INHIBIT ETOPOSIDE-INDUCED APOPTOSIS IN A MURINE PRE-B-CELL LINE

Murine bone marrow-derived hemopoietic cells, dependent on interleukin (IL)-3 for their growth in culture, undergo programmed cell death, or apoptosis, upon cytokine withdrawal. The topoisomerase II inhibitor etoposide causes a more rapid onset of apoptosis in the IL-3-dependent cell line BAF3, deprived of IL-3. This acceleration of apoptosis by etoposide is prevented by inhibitors of RNA and protein synthesis and by the nucleases inhibitor aurintricarboxylic acid. The presence of IL-3 or overexpression of the oncogene bcl-2 caused a marked delay in the induction of apoptosis by etoposide, acting in a cooperative manner. The time at which the apoptotic program is irreversible is close to the induction of endonuclease activity as indicated by the effect of the delayed addition of either IL-3 or aurintricarboxylic acid on the onset of apoptosis, suggesting the importance of endonuclease activation in the development of apoptosis in hemopoietic cells.