1968 Volume 20 Issue 1 Pages 25-44
Changes of the activity of glucose-6-phosphatase (G-6-Pase) was observed ultracytochemically in the hepatic cells of the male Sprague-Dawley rats treated with 3'-MeDAB up to 35 weeks.
In the normal hepatic parenchymal cells the G-6-Pase activity was positive in the rough-surfaced endoplasmic reticulum (ER), the smooth-surfaced ER including the one around the glycogen area and the transitional elements, and the nuclear envelope. The enzymatic activity was not observed in the Golgi apparatus, coated vesicles, multivesicular bodies and plasma membranes. The endothelial cells and epithelial cells lining the bile duct system did not reveal any enzymatic activity and only the hepatic parenchymal cell showed the enzymatic activity.
It was evident that the enormously proliferated tubular smooth-surfaced ER in the hepatic cells of treated rats was still positive for the G-6-Pase activity. It should be emphasized that this proliferation of the smooth-surfaced ER was evident only in the early and intermediate stages (up to 24 weeks) of the hepatocarcinogenesis. In the hepatocellular hepatoma cells the area of the proliferated smooth-surfaced ER could not be encountered, although in some cells of the early hepatoma remnants of the smooth-surfaced ER could be seen occasionally.
In hepatocellular hepatoma cells, the two types of the cell were observed, that is, the clear cell and the dark cell. In both cells the G-6-Pase was demonstrable, although the enzymatic activity was rather weak and there was quite a degree of cell to cell variation in the activity. In some hepatoma cells an amount of the rough-surfaced ER appeared to be increased, however, generally speaking, there seemed to be cell to cell variation in an amount of the rough-surfaced ER also.
The young proliferated oval cells arising from the cholangiole and the cholangioma cells did not reveal any G-6-Pase activity.
These findings strongly suggest the fact that the hepatocellular hepatoma arises from the hepatic parenchymal cells, while the cholangioma from the oval cells from the cholangiole.
It was of great interest to note that the proliferation of the smooth-surfaced ER did not persist through the carcinogenesis of the hepatocellular hepatoma and was ceased at a certain stage. The hepatoma cells seem to have lost the capacity of the smoothsurfaced ER proliferation. It is highly likely that the hepatic cell turns into a neoplastic cell following the cessation of the smooth-surfaced ER proliferation. In this connection, an elucidation of the mechanism of the biogenesis of the membrane system in the cell warrants a special attention in the field of the cellular mechanism of the hepato-carcinogenesis in the future.
Supported by grants from the Anna Fuller Fund, the Jane Coffin Childs Memorial Fund (Project # 196) and the Japanese Government (Gann # 94157) administered by Prof. K. Ogawa.
