HEPATIC GROWTH INDUCED BY INJECTION OF THE LIVER GROWTH-FACTOR INTO NORMAL RATS

Normal Wistar rats injected with the liver growth factor (LGF), a mito gen specific for liver cells, experienced hepatic growth. LGF shows tw o peaks of activity in vivo, both of them mitogenic. Rats injected eit her with 6.8 ng or 3.9 mu g LGF/rat every 3-4 days experienced liver g rowth showing a see-saw profile. Dry liver weight usually peaked at da y 2 (mu g doses) or at day 3 (ng doses) after each injection, with inc reases of about 30% over controls. Liver DNA synthesis, measured by [H -3]-thymidine incorporation, peaked 24 h after LGF injection at both d oses. Liver protein synthesis, measured by [(14)]C-leucine incorporati on, usually peaked 24 h after DNA synthesis maximums. Mitogen-stimulat ed cells were also assessed by immunohistochemical staining for prolif erating cell nuclear antigen in livers of LGF-injected rats. Rats inje cted with rat serum albumin purified from normal rats to serve as cont rols showed a 6% increase in dry liver weight, but when serum albumin from 3-day fasted rats was injected instead, the increase was not stat istically significant. The mild effect of rat serum albumin could be d ue to the lipid content of the solutions injected, but the level of li pids/mg protein in LGF solutions was half that determined with serum a lbumin from 3-day fasted rats. From the microscopic and ultramicroscop ic studies carried out in rat livers injected with LGF at each dose, w e observed: (1) an increase in the number of hepatocytes undergoing mi tosis; (2) transient increases in lipid and glycogen contents, as occu r after liver resection; (3) no signs of degeneration, such as the app earance of amyloids or fibrosis; (4) no increase in lysosome number, a s in hepatotoxicity; (5) no alterations in endothelial or Kupffer cell s; and (6) no ultrastructural signs of degeneration either in cytoplas mic organelles (rough endoplasmic reticulum, mitochondria) or in nucle i. One year after LGF injection, rat liver, pancreas, kidneys and sple en were normal, with no signs of degeneration or onset of fibrosis.