Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma

Aim: The aim of this study is to assess the poly ADP-ribosylation activity in human hepatocellular carcinoma (HCC) and in liver cirrhosis (LC) as compared to the activity in normal livers (NL). Methods: Hepatocellular carcinoma and LC tissues were sampled from 19 patients with HCC. Normal liver tissue was obtained from 19 patients with metastatic liver cancer. Poly ADP-ribosylation activity of these tissues was measured by using [P-32]-adenylate nicotinamide adenine dinucleotide (NAD)-incorporation into the 116-kDa protein. Nicotinamide adenine dinucleotide glycohydrolase activity of these tissues was determined with thin layer chromatography. The immunohistochemical expression of Ki-67 was also assessed as a parameter of cell proliferative activity. Results: The poly ADP-ribosylation of the 116 kDa protein was significantly increased in patients with HCC and LC as compared with NL (P<0.0001, P<0.05, respectively) and was inhibited by poly (ADP-ribose) polymerase inhibitors in a dose-dependent manner. There was no significant difference in NAD glycohydrolase activity among the three groups. A significant correlation was found between the Ki-67 positive cell rate and the relative radioactivity of poly ADP-ribosylation in HCC patients (r=0.794, P<0.0001). The poly ADP-ribosylation of the 116 kDa protein of LC was significantly higher in patients who had recurrences of HCC after hepatic resection than in patients without recurrence (P<0.05). Conclusion: Poly ADP-ribosylation of the 116 kDa protein in HCC patients might be enhanced with its proliferative activity, and poly ADP-ribosylation of the same protein in LC patients might be a useful parameter of carcinogenic potential for predicting HCC recurrence after hepatectomy in patients who have had HCC. (C) 2001 Blackwell Science Asia Pty Ltd.