Opposite effects of cell differentiation and apoptosis on Ap(3)A/Ap(4)A ratio in human cell cultures

The biological role of diadenosine oligophosphates (DAOP) remains obscure in spite of numerous attempts to solve this enigma. It is known that Ap(3)A contrary to Ap(4)A accumulates in human cultured cells treated with interferons (IFNs) alpha or gamma. Since IFNs are considered as antiproliferative regulators, we assumed that different cell status may be associated with varying intracellular levels of DAOP. Promyelocytic human cell line HL60 induced by phorbol ester (TPA) to differentiate to macrophage-like cells in culture exhibits a profound loss of proliferative potential. Here we have shown a 4-5-fold increase in Ap(3)A concentration in HL60 cells induced by TPA, similar to the effect of IFN, while the Ap(4)A concentration remained unchanged. On the contrary, in cells undergoing apoptosis induced by VP16, a topoisomerase II inhibitor, the Ap(3)A concentration considerably decreased, while the Ap(4)A concentration increased. These findings combined with earlier results suggest an involvement of the Ap(3)A/Ap(4)A ratio in signal transduction pathways controlling the cell status. (C) 1997 Federation of European Biochemical Societies.