Induction of Deoxyribonucleic Acid Synthesis in the Liver of the Intact Animal

Abstract Based in part on observations made in blood-mixing experiments with intact and 70 and 90% hepatectomized rats, a mixture of chemicals has been devised that induces nuclear DNA formation and mitosis in the parenchymal liver cells of the unoperated animal. The mixture (TAGH solution) contains 3,3',5-triiodo-l-thyronine (triiodothyronine), amino acids, glucagon, and heparin. Each component of the stimulatory solution contributes to the enhancement in DNA synthesis but triiodothyronine is the single most important constituent. Given with the AGH solution (amino acids, glucagon, and heparin), as little as 2 µg of the hormone has a detectable effect and 10 µg is about two-thirds as effective as 100 µg or 2 mg. The time curve of the response of unoperated rats to the TAGH solution is the same as after 70% hepatectomy. With both stimuli, liver DNA formation begins at 14 hours. Unoperated rats can be initially treated with triiodothyronine, however, so that DNA synthesis is already high at 10 hours from the start of the infusion of the AGH solution. Several pieces of evidence are given to show that the TAGH solution does not induce DNA replication by damaging some of the cells of the intact liver. The TAGH solution, just as 70% hepatectomy, causes in the liver an increase in the rate of ribosome formation, an accumulation of glycerides, and changes in fatty acid composition. Unlike partial hepatectomy, however, the solution does not produce rises in the rates of synthesis of serum albumin or of total hepatic protein.