Rapid inhibition of DNA synthesis in hepatocytes from regenerating rat liver by serum from patients with fulminant hepatic failure

Abstract

The acute effects of serum from patients with fulminant hepatic failure (FHF) on isolated hepatocytes from normal and regenerating rat livers were investigated. DNA and protein synthesis monitored by following the incorporation of [6-3H]-thymidine and [U-14C]-1-leucine into acid-precipitable material was accelerated in hepatocytes from regenerating livers. A specific inhibitory effect of FHF serum on DNA synthesis in hepatocytes from regenerating livers was found. DNA and protein synthesis was inhibited in normal rat hepatocytes by normal serum, the inhibition being less with FHF serum. Cell integrity assessed by leakage of lactate dehydrogenase was not affected by normal or FHF serum. These findings may explain the reduced rate of hepatic regrowth in patients with FHF. Identification of the substances involved will assist in the design of artificial liver support systems and may improve prognosis in this condition.