EFFECTS OF FULMINANT HEPATIC-FAILURE SERUM ON HEPATIC DNA-SYNTHESIS IN NORMAL AND PARTIALLY HEPATECTOMIZED RATS

The effects of fulminant hepatic failure (FHF) serum on DNA synthesis were investigated in vivo in partially hepatectomized and normal rats. Significant inhibition of H-3-thymidine incorporation was obtained on injection of FHF serum into rats 20-23h post-operation, the time of maximal DNA synthesis (median 166 dpm/mu-g DNA per h, range 81-270, n = 18 versus control 203, range 136-255, n = 9, P < 0.01). Inhibition was also present (median 154, range 82-219 dpm/mu-g DNA per h, n = 12, p < 0.01) on injection of normal serum which may reflect the non-dividing state of the hepatocytes in normal liver. The effects of FHF serum were shown to be associated with a serum ultrafiltrate fraction lower than 10 kD. Studies in normal rats showed no stimulation of H-3-thymidine incorporation from the initial low level, and hence no initiation of DNA synthesis. Thus the overall effect of circulating substances in FHF serum is one of inhibition which may counteract the effects of any hepatic regenerative stimulator substances.