Early increase in diadenosine tetraphosphate in regenerating rat liver.

Diadenosine tetraphosphate (Ap4A), a candidate for a signal molecule in the induction of DNA synthesis, was measured in regenerating livers of young adult rats at 12 and 24 h and of older rats at 24 h after partial hepatectomy. dATP and dTTP levels, which indicate the degree of proliferation in the livers, were determined by high-performance liquid chromatography and an enzymatic method, respectively. The Ap4A levels were increased in the beginning of DNA synthesis. In young rats the levels were about 140% of those of unoperated rats and in older rats about 300%. This increase was considerably smaller than that found in another study comprising two regenerating rat livers excised 20 h after partial hepatectomy, but still supports the hypothesis that Ap4A might take part in the onset of proliferation. The greater Ap4A increase in older rats may suggest a possible need for a stronger triggering mechanism to start proliferation in aged tissue. However, the experiments do not prove a function for Ap4A in the induction of DNA synthesis and it cannot be excluded that Ap4A is a product of an independent reaction.