AN EARLIER PROLIFERATIVE RESPONSE OF HEPATOCYTES IN GAMMA-GLUTAMYL-TRANSFERASE POSITIVE FOCI TO PARTIAL-HEPATECTOMY

One of the hallmarks of initiated hepatocytes is their resistance to s everal hepatotoxins. This property forms the basis for their selective growth under conditions which are inhibitory to the non-initiated hep atocytes. Selective growth of initiated hepatocytes also occurs, albei t at a low level, in initiated rat liver without exposure to any known promoting regimen and/or in the absence of any known selective pressu re to which initiated hepatocytes can possibly be resistant. This latt er phenotypic property of initiated hepatocytes was further characteri zed by comparing the kinetics of response of hepatocytes in gamma-glut amyl transferase positive foci and in the surrounding liver to 2/3 par tial hepatectomy both in the presence and in the absence of a promotin g regimen. Male Fischer 344 rats (130-150 g) were initiated with a sin gle dose of diethylnitrosamine and 1 week later they were placed on ei ther a semi-synthetic basal diet or a promoting diet containing 1% ero tic acid. Partial hepatectomy was performed 15 weeks after initiation and animals from both groups were killed at 12, 16, 20, 24, 30, 36, 48 , 72 or 96 h after operation. Each animal received a pulse of H-3-labe lled thymidine 1 h prior to killing. Autoradiographic studies revealed that hepatocytes in gamma-glutamyl transferase positive foci in the l ivers of rats fed the basal diet were significantly labelled at 16 h p ost-partial hepatectomy while surrounding hepatocytes were still virtu ally quiescent (LI 12.7 +/- 4.7 versus 1.2 +/- 0.5%, respectively). Hi gher labelling index in foci compared to the surrounding liver was als o seen at 20 h post-PH (36.9 +/- 2.6 versus 21.5 +/- 2.4). Similar ear lier response of hepatocytes in gamma-glutamyl transferase positive fo ci was also seen in initiated rats exposed to dietary erotic acid. In addition, erotic acid treatment appears to have imposed a slight delay on the entry of hepatocytes in the surrounding liver into 'S' phase a nd thereby enhancing the differential of growth response between these two populations.