Variation of (2'-5')oligo(adenylate) synthetase activity during rat-liver regeneration

The interferon-induced double-stranded RNA-activated (2'-5')oligo(adenylate) synthetase converts ATP into (2'-5')oligo(adenylate) [(2'-5')oligo(A)] and pyrophosphate. In turn, (2'-5')oligo(A) activates a latent endoribonuclease which cleaves single-stranded RNA. (2'-5')Oligo(A) synthetase activity has been characterized in liver cells of normal and germ-free rats. This enzyme is predominantly nuclear. After partial hepatectomy, (2'-5')oligo(A) synthetase activity decreased rapidly (after 10 h) and markedly to a minimum of 25% of the control after 20 h. This decrease was followed by a slow restoration of the activity. No such change was observed in sham-operated animals. This important decrease of enzymatic activity occurred during the first few hours of liver regeneration (6-24 h). This period corresponds also to the prereplicative and replicative (18-24 h after hepatectomy) phases of DNA. Detailed kinetics indicated that the loss of (2'-5')oligo(A) synthetase activity preceded the onset of the incorporation of tritiated thymidine in DNA and was minimal when the rate of DNA synthesis was maximal. These results and those obtained in culture of cells in vitro are compatible with the hypothesis that the (2'-5')oligo(A) system participates in the negative control of cell proliferation.