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

J Gastroenterol Hepatol. 2001 Mar;16(3):338-44. doi: 10.1046/j.1440-1746.2001.02378.x.

Abstract

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 [32P]-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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / metabolism*
  • Female
  • Humans
  • Immunoblotting
  • Ki-67 Antigen / metabolism
  • Liver Cirrhosis / metabolism*
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged
  • NAD+ Nucleosidase / metabolism
  • Neoplasm Recurrence, Local
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Reference Values

Substances

  • Ki-67 Antigen
  • Poly Adenosine Diphosphate Ribose
  • NAD+ Nucleosidase