Alpha 2b-interferon inhibits rat liver regeneration after partial hepatectomy without affecting thymidine kinase activity.
The effect of alpha 2b-interferon administration on liver regeneration after partial hepatectomy in male Wistar rats was examined 24 hours after the operation. Tritium thymidine incorporation into liver DNA, liver mass restitution, mitotic index, and nuclear expression of proliferating cell nuclear antigen were determined as indexes of hepatic proliferation. Both early and late alpha 2b-interferon administration, 2 and 12 hours, respectively, after partial hepatectomy, at a dose of 3.3 x 10(4) IU per kg body weight, suppressed tritium thymidine incorporation and liver mass restitution (p < 0.001) when compared with that in untreated partially hepatectomized rats. The enzyme thymidine kinase (EC 2.7.1.21), a rate-determining enzyme of DNA biosynthesis, has been implicated in the suppression of proliferation in interferon-treated cell cultures. However, in the above-mentioned in vivo model of controlled cellular proliferation, thymidine kinase activity was not affected by alpha 2b-interferon administration, whereas DNA biosynthesis was inhibited. These findings, in contrast to previous observations in in vitro models, show that the inhibition of the in vivo liver regeneration by alpha 2b-interferon is not due to the inhibition of thymidine kinase activity. The expression of the cell cycle-related genes' products c-myc, p53, and c-erbB-2 proteins--which increase during the prereplicative phase that precedes DNA synthesis--was affected by interferon administration, being in accordance with liver proliferative status.
Theocharis
S E
SE
Department of Experimental Pharmacology, School of Medicine, University of Athens, Greece.
Margeli
A P
AP
Tsokos
M G
MG
D000818:Animals; D001769:Blood / Q000378:metabolism; D002455:Cell Division; D006498:Hepatectomy / Q000379:methods*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013937:Thymidine Kinase / Q000378:metabolism*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013937:Thymidine Kinase