Contribution of primary cultures of adult human hepatocytes to the pathophysiology of hepatocellular carcinoma.
OBJECTIVE
The mechanisms of hepatocarcinogenesis are still poorly understood. The development of hepatocellular carcinoma has recently been shown to be associated with increased DNA synthesis in cirrhosis. The aim of this work was to determine whether the high rate of hepatocyte regeneration observed in cirrhotic liver with hepatocellular carcinoma is associated with the presence of a growth factor that could be detectable in the serum.


METHODS
Adult human hepatocytes in primary culture, allowing the evaluation of the release of circulating hepatotrophic factors, were used. These cultures were treated for 48 h with serum from patients with cirrhosis with and without hepatocellular carcinoma, from patients with liver metastasis, and from healthy subjects. The rate of DNA synthesis in these cultures was assessed by measuring the amount of [3H]-thymidine incorporation into genomic DNA.


RESULTS
On average, the synthesis of DNA was increased 2.5-, 2.2-, 2.1-, and 2.3-fold, respectively, in response to serum from patients with cirrhosis with hepatocellular carcinoma, from patients with cirrhosis without hepatocellular carcinoma, from patients with liver metastasis, and from healthy subjects.


CONCLUSIONS
We conclude that the hepatotrophic activity of the serum is not significantly different in patients with cirrhosis with or without hepatocellular carcinoma. These results suggest that the increased DNA synthesis in hepatocytes of cirrhotic liver with hepatocellular carcinoma might be due to proliferative factor(s) acting by paracrine or autocrine pathways.
Blanc
P
P
INSERM, Unité 128, CNRS, Montpellier, France.
Desprez
D
D
Fabre
J M
JM
Pageaux
G
G
Daures
J P
JP
Larrey
D
D
Saint-Aubert
B
B
Michel
H
H
Maurel
P
P
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D016022:Case-Control Studies; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008113:Liver Neoplasms / Q000150:complications / Q000503:physiopathology* / Q000556:secondary; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012016:Reference Values
D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D004247:DNA