FLUCTUATION OF VARIOUS CELL POPULATIONS AND THEIR CHARACTERISTICS DURING AZO-DYE CARCINOGENESIS

Abstract

Fluctuaton in population of cells and the alteration of cell characteristics in liver of rats during the early stage of carcinogenesis by 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) were studied histologically, ultrastructurally, and biochemically.
After commencement of 3'-Me-DAB administration at a concentration of 0.06%, the initial change in liver cells was the pronounced degeneration of hepatocytes, and consequently the original hepatocytes gradually disappeared, being replaced by the proliferation of cholangiolar cells (the so-called oval cells) after 2 weeks of ingestion of 3'-Me-DAB. Such quantitative change in cellular population was represented by the decreases in liver weight, glucose-6-phosphatase activity, and content of proteinbound dye. Oval cell proliferation in the periportal area of hepatic lobules reached a maximum in the 4th week occupying about one-half of each lobule and, thereafter, the small hepatocytes transformed from the oval cells appeared in the periportal area. The ultrastructural characteristics of these cells revealed various transitional phases toward hepatocytes. They extended to the central vein of most lobules, increasing in their volume, and by the 11th week, the original hepatocytes were almost completely replaced by these renewed hepatocytes. It seemed that the period of appearance of the renewed small hepatocytes corresponded to that of appearance of α-fetoprotein in the sera.