Cyclic adenosine monophosphate promotes cell survival and retards apoptosis in a factor-dependent bone marrow-derived...

Hemopoietic growth factors promote cell survival, proliferation and differentiation, but whether these processes, which often occur in concert, are mediated through the same or different receptor signaling mechanisms is not known. Using the bone marrow-derived IL-3-dependent cell line, 32D, we show that dibutyryl cyclic adenosine monophosphate (dbcAMP) retards the rapid loss of viable cells seen in the absence of IL-3. This effect is shown to be concentration-dependent and detectable within 16 hours of culture and is not associated with cell differentiation. At earlier times (2 to 7 hours), when no significant changes in cell numbers were observed, dbcAMP stimulated the reduction of dimethylthiazoldiphenyl tetrazolium bromide (MTT), and this effect was indistinguishable from that seen with IL-3. In contrast, control cells deprived of growth factor showed a decline in MTT response over this period. The effect of dbcAMP in maintaining cell viability and MTT responsiveness was associated with a concentration-dependent inhibition of 3H-thymidine incorporation into DNA, and retardation of the intranucleosomal cleavage of DNA that is associated with apoptosis. These results suggest that in 32D cells, cAMP can act to promote cell survival and retard apoptosis, quite independently of cell proliferation, by stimulating the activity of mitochondrial enzymes involved in MTT reduction.