DNA Synthesis in Rat Liver during Early Stages of Azo Dye-induced Hepatocarcinogenesis

Summary DNA synthesis of various cell types of liver tissue from rats fed 3′-methyl-4-dimethylaminoazobenzene was studied by autoradiography after the injection of thymidine-methyl- 3 H. Livers of identical animals were used by Sneider, Bushnell, and Potter for a biochemical study involving the separation of nuclei into two classes, and the results obtained by these 2 independent methods are compared. In agreement with biochemical results, the numerical proportions of various liver cell types were altered prior to changes in DNA synthesis. DNA synthesis of bile duct cells began to increase 10 days after the start of azo dye feeding, reaching a peak on Day 14. Hepatocytes and mesenchymal cells started DNA synthesis with a lag and showed maximum proliferation on Day 17. Hemopoietic cells, showing a high labeling index, were demonstrable in the liver from Day 14 until the end of the experiment on Day 42. Prolongation of the interval between injection of tritiated thymidine and sacrifice resulted in a drop in the labeling index. Hemopoietic and bile duct cells exhibited a steep decrease, while hepatocytes and mesenchymal cells showed less reduction of the labeling index. These autoradiographic results confirm the value of the biochemical method of separating “hepatocytic” and “nonhepatocytic” nuclei from liver tissue, provided that these experiments are mainly concerned with hepatocytes. Proliferation dynamics of various subpopulations of nonhepatocytic cells during early stages of liver carcinogenesis are highly heterogeneous and require, in addition to biochemical investigation, a detailed morphological and autoradiographic analysis.