Thymidine kinase: an inexpensive index of liver regeneration in a large animal model

Abstract

Most studies of liver regeneration have been restricted to small animals because of the cost of assessment of DNA synthesis by the standard method of thymidine incorporation in vivo. This paper presents the use of thymidine kinase as an inexpensive measure of regeneration in large animals. The use of the large model is advantageous because of the availability of serial blood and tissue samples from the same animal. Initially, the responses in thymidine kinase and thymidine incorporation over a period of 96 hr were shown to correspond well in rats subjected to 68% and 34% hepatectomy. Any delays could be attributed to different times of operation. A reproducible technique for 50% partial hepatectomy in the pig was developed, and the animals were studied by daily open liver biopsy for 7 days. The responses in thymidine kinase activity and mitotic indices showed tha peak regeneration occurred at 3-4 days. Levels of aspartate amino transferase were elevated sevenfold after partial hepatectomy but returned to normal within 96 hr. The levels of alkaline phosphatase and bilirubin were unaltered, confirming that the biliary drainage had not been compromised. This study offers the pig as another suitable model for the study of liver regeneration and thymidine kinase activity as a suitable index.