Effect of interferon-alpha2b administration on rat liver regeneration after partial hepatectomy.
The purpose of the present study was to delineate the effect of interferon-alpha2b (IFN-alpha2b) administration on the liver regenerative capacity after partial hepatectomy in rats. The administration of IFN-alpha2b simultaneously with partial hepatectomy did not affect hepatic proliferation in a statistically significant manner. When IFN-alpha2b was administered either 2 or 12 hr postoperatively, an inhibition of hepatocyte proliferation was observed 24 hr postoperatively, while at further time intervals up to 48 hr, DNA synthesis remained similar to that observed in the simply partially hepatectomized rats. The enzyme thymidine kinase (TK), has been implicated in the suppression of proliferation in interferon-treated cell cultures. In all IFN-alpha2b-treated groups of rats, alterations of TK activity were observed without being correlated to the liver regenerative status. Additionally, the administration of the polyamine putrescine in partially hepatectomized rats treated at the time of surgery with IFN strongly enhanced TK activity, but did not affect DNA biosynthesis. In the above-mentioned in vivo model of controlled cellular proliferation, the administration of IFN-alpha2b affected the rate of hepatocyte proliferation depending on the time of its administration; this effect was not correlated to the enzymatic activity of TK, as inhibited TK activity is responsible for the suppressed DNA synthesis in in vitro systems.
Theocharis
S E
SE
Department of Histology and Embryology, Medical School, University of Athens, Greece.
Margeli
A P
AP
Skaltsas
S D
SD
Skopelitou
A S
AS
Mykoniatis
M G
MG
Kittas
C N
CN
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006498:Hepatectomy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013937:Thymidine Kinase / Q000378:metabolism; D013997:Time Factors
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004247:DNA; D013937:Thymidine Kinase; D011700:Putrescine