The enzyme gamma-glutamyl transpeptidase (gamma-glutamyl transferase, GT-ase, E.C. 2.3.2.2) behaves as a Marker in the mechanism of chemical carcinogenesis in rat liver. There are, however, in rat liver at least two other forms of this enzyme, which may or may not, play a role in the cancerous process: a) an inducible, short-lived, GT-ase and, b) a constitutive GT-ase bound, under normal conditions, only to epithelial cells or biliary ducts. The aim of this work is to isolate and purify to homogeneity these three forms of GT-ase from rat liver and investigate their physico-chemical differences, if such exist. When this is accomplished we shall be able to understand much better the role of the Marker GT-ase in the process of carcinogenesis and will be able to use it as a reliable tool to investigate important, but at the present still completely obscure, fundamental questions of the mechanism of hepatocarcinogenesis: 1. To identify and characterize the cells in which carcinogens initiate carcinogenesis and start the line of cells from which eventually malignant cells develop; 2. to observe temporal sequence and determine causal connection between essential steps leading to cancer development, and 3. to determine half-lives of these forms of GT-ase and how they may change under the influence of carcinogens, this last objective possibly answering the nature of the underlying basic nature of carcinogenic process in rat liver and other organs.
NIH ExPorter
NIH ExPorter