Hepatic growth induced by injection of the liver growth factor into normal rats.

Normal Wistar rats injected with the liver growth factor (LGF), a mitogen specific for liver cells, experienced hepatic growth. LGF shows two peaks of activity in vivo, both of them mitogenic. Rats injected either with 6.8 ng or 3.9 micrograms LGF/rat every 3-4 days experienced liver growth showing a see-saw profile. Dry liver weight usually peaked at day 2 (microgram doses) or at day 3 (ng doses) after each injection, with increases of about 30% over controls. Liver DNA synthesis, measured by [3H]-thymidine incorporation, peaked 24 h after LGF injection at both doses. Liver protein synthesis, measured by [14]C-leucine incorporation, usually peaked 24 h after DNA synthesis maximums. Mitogen-stimulated cells were also assessed by immunohistochemical staining for proliferating cell nuclear antigen in livers of LGF-injected rats. Rats injected with rat serum albumin purified from normal rats to serve as controls showed a 6% increase in dry liver weight, but when serum albumin from 3-day fasted rats was injected instead, the increase was not statistically significant. The mild effect of rat serum albumin could be due to the lipid content of the solutions injected, but the level of lipids/mg protein in LGF solutions was half that determined with serum albumin from 3-day fasted rats. From the microscopic and ultramicroscopic studies carried out in rat livers injected with LGF at each dose, we observed: (1) an increase in the number of hepatocytes undergoing mitosis; (2) transient increases in lipid and glycogen contents, as occur after liver resection; (3) no signs of degeneration, such as the appearance of amyloids or fibrosis; (4) no increase in lysosome number, as in hepatotoxicity; (5) no alterations in endothelial or Kupffer cells; and (6) no ultrastructural signs of degeneration either in cytoplasmic organelles (rough endoplasmic reticulum, mitochondria) or in nuclei. One year after LGF injection, rat liver, pancreas, kidneys and spleen were normal, with no signs of degeneration or onset of fibrosis.