Correlation of intracellular diadenosine triphosphate (AP3A) with apoptosis in Fhit-positive HEK293 cells

The pro-apoptotic Fhit tumor suppressor protein binds and hydrolyses diadenosine triphosphate (A(P3)A) and diadenosine tetraphosphate (A(P4)A) in vitro. We have measured the level of both these nucleotides in Fhit-positive HEK293 cells exposed to various apoptosis inducers. Cold shock, anti-Fas, cadmium ions and etoposide all increased the basal level of ANA of 0.500 pmol/10(6) cells by about 50%. However, the corresponding increases in A(P3)A from a basal 0.079 pmol/10(6) cells correlated closely with the degree of apoptosis produced, tip to a maximum of 0.510 Pmol/10(6) cel is with etoposide. These results support the view that AP3A is the in vivo Fhit ligand and that an inhibition of Fhit activity is a key element in Fhit-mediated apoptosis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.