Diadenosine 5',5'-P1,P4-tetraphosphate (AP4A) levels under various proliferative and cytotoxic conditions in several mammalian cell types

Diadenosine 5',5'-P1,P4-tetraphosphate (Ap4A) has been proposed as an intracellular signal for growth. In order to test this hypothesis Ap4A levels were followed in several cell types under various conditions. Quiescent dog thyroid cells in a primary culture were induced to proliferate by addition of a mixture of epidermal growth factor, thyrotropin and foetal calf serum; V79 cells were synchronized by serum depletion then stimulated to proliferate by addition of foetal calf serum. Protein and DNA synthesis increased in both cases, although no significant changes in Ap4A levels per cell could be demonstrated. HeLa D98/AH2 and L929 cells were treated with human recombinant tumour necrosis factor alpha which caused marked cell death. This was measured by a decrease in DNA content and a release into extracellular medium of incorporated radioactive precursor. No concomitant variations in Ap4A concentrations could be observed under these conditions. The data from these various systems do not support the hypothesis that changes in Ap4A levels regulate cellular proliferation.