ALPHA(2B)-INTERFERON INHIBITS RAT-LIVER REGENERATION AFTER PARTIAL-HEPATECTOMY WITHOUT AFFECTING THYMIDINE KINASE-ACTIVITY

The effect of alpha(2b)-interferon administration on liver regeneratio n after partial hepatectomy in male Wistar rats was examined 24 hours after the operation. Tritium thymidine incorporation into liver DNA, l iver mass restitution, mitotic index, and nuclear expression of prolif erating cell nuclear antigen were determined as indexes of hepatic pro liferation. 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 incorpo ration and liver mass restitution (p < 0.001) when compared with that in untreated partially hepatectomized rats. The enzyme thymidine kinas e (EC 2.7.1.21), a rate-determining enzyme of DNA biosynthesis, has be en implicated in the suppression of proliferation in interferon-treate d cell cultures. However, in the above-mentioned in vivo model of cont rolled cellular proliferation, thymidine kinase activity was not affec ted by alpha(2b)-interferon administration, whereas DNA biosynthesis w as inhibited. These findings, in contrast to previous observations in in vitro models, show that the inhibition of the in vivo liver regener ation by alpha(2b)-interferon is not due to the inhibition of thymidin e kinase activity. The expression of the cell cycle-related genes' pro ducts c-myc, p53, and c-erbB-2 proteins-which increase during the prer eplicative phase that precedes DNA synthesis-was affected by interfero n administration, being in accordance with liver proliferative status.