THE EFFECT OF EXTRAHEPATIC CHOLESTASIS ON LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY IN THE RAT

Liver regeneration after partial hepatectomy was studied in four group s of rats: control rats (n = 12), rats with 1 week of common bile duct obstruction (n = 11), rats with restoration of bile flow after 1 week of obstruction (n = 9) and a sham-operated group (n = 7). Parameters of DNA synthesis - thymidine kinase activity and in vivo bromodeoxyuri dine incorporation - were measured at partial hepatectomy (T = 0), and 24 and 48 h after partial hepatectomy. During common bile duct obstru ction, DNA synthesis was already stimulated at T = 0, but partial hepa tectomy in common bile duct obstruction rats induced a delayed DNA syn thesis. After 1 week of restoration of bile flow, normal DNA synthesis had returned at T = 0, but DNA synthesis after partial hepatectomy wa s still delayed. The sham-operated rats showed a normal regeneration r esponse after partial hepatectomy assessed by bromodeoxyuridine incorp oration but delayed as assessed by thymidine kinase activity, partly d ue to the impaired physical condition of the animals. The present data support the hypothesis that during cholestasis, regeneration promotin g, and inhibitory factors accumulate in the liver, their balance deter mining whether regeneration after partial hepatectomy will occur in a normal, enhanced or delayed way.