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


CONCLUSIONS
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.
Shiobara
M
M
First Department of Surgery, School of Medicine, Chiba University, Japan.
Miyazaki
M
M
Ito
H
H
Togawa
A
A
Nakajima
N
N
Nomura
F
F
Morinaga
N
N
Noda
M
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D019394:Ki-67 Antigen / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009244:NAD+ Nucleosidase / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D012016:Reference Values
D019394:Ki-67 Antigen; D011064:Poly Adenosine Diphosphate Ribose; D009244:NAD+ Nucleosidase