DNA polymerases and Ki-67 nuclear antigen are induced in correlation with the resected mass of rat liver up to 90%

Abstract 

Background and aims: We studied the regeneration potential by measuring induction of DNA polymerases in the remnant rat liver after a partial hepatectomy (PHx) that is maximal but compatible with survival. Methods: The regenerating rat liver was obtained after the 90% PHx. The induction of activities of DNA polymerase α, δ, and ɛ were measured after partial purification. The Ki-67 nuclear antigen was also detected histochemically. These parameters were compared with those after both 30% and 70% PHx. Results: The 90% hepatectomy resulted in the strong inductions of DNA polymerase α, δ, and ɛ, at 48 h after operation, in association with increases in wet weight and total DNA in the remnant liver. The enzyme induction was much higher after 90% PHx than after 30% and 70% hepatectomy, in correlation with the resection volume. At 48 h after 90% hepatectomy, the Ki-67 positive cells increased up to 47.2% of hepatocytes in the remnant liver. Conclusion: The higher induction of replication enzymes by 90% hepatectomy reflects more cells entering mitogenic cell cycle, which supports the fast regeneration of the remnant liver. The number of proliferating hepatocytes is stringently controlled by an unknown mechanism sensing the mass of resected liver parenchyma.