Appearance of an inhibitory cell nuclear antigen in rat and human serum during variable degrees of hepatic regenerative activity

AIM To determine whether proliferating cell nuclear antigen (PCNA) is present in the peripheral circulation and whether PCNA levels correlate with enhanced regenerative activity. METHODS In animal studies, adult male Sprague Dawley rats ( n =3-4/group) were sacrificed at 0, 12, 24, 36, 48, 72 and 96 hours following 70% partial hepatectomy. At each interval, sera were analyzed by Western blot for PCNA by two monoclonal antibodies (PC 10 and 19F 4). In human studies, sera from 4 patients with liver cirrhosis and 4 healthy controls were tested in a similar manner. RESULTS The PC 10 monoclonal antibody identified a protein with a molecular mass of 120 KD which remained stable in rat sera for 24 hours following partial hepatectomy, then increased 1 5 fold at 48 hours prior to returning to baseline at 96 hours after partial hepatectomy. However, it was not detected in the sera of patients with or without liver disease. In the 19F 4 monoclonal antibody, a protein with a molecular mass of approximately 46 KD was found. which was present in rat sera prior to partial hepatectomy and for 12 hours after surgery. Thereafter, levels fell by approximately 50% at 24 hours, 65% at 36 hours and 75% at 48 hours where they remained until 96 hours after partial hepatectomy. The decrease in levels correlated with the extent of partial hepatectomy. In human sera, the appearance of this inhibitory cell nuclear antigen (ICNA) was higher in the sera of patients with cirrhosis than in healthy controls. CONCLUSION The PC 10 monoclonal antibody can detect a protein in the circulation when active hepatic regenerative activity is taking place. The 19F 4 monoclonal antibody, however, identifies a protein in both rat and human sera that inversely correlates with hepatic regenerative activity. This protein which is tentatively referred to as inhibitory cell nuclear antigen (ICNA) may be used in documenting the extent of suppression of hepatic regeneration.