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Demonstration of Glucose 6-Phosphatase Activity in the Oval Cells of Rat Liver and the Significance of the Oval Cells in Azo Dye Carcinogenesis¹

Department of Pathology, Sapporo Medical College, Chuo-ku, Minami 1, Nishi 17, Sapporo, Hokkaido, Japan

Glucose 6-phosphatase activity was studied histochemically in the oval cells of rat livers during the early stage of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene. Short-period perfusion fixation of the liver preserved both the ultrastructure of the liver cells and glucose 6-phosphatase activity excellently throughout the whole hepatic tissue. Under light microscopic examination of the liver of rats fed the azo dye diet, glucose 6-phosphatase activity was found in the oval cell proliferating area in varying degrees. The electron microscopic study demonstrated that the oval cells formed ductular structures with elaborated basal laminae, and were occasionally found within the space of Disse between the hepatocytes. Ultrastructurally, some oval cells were identical to bile ductular cells, while others showed various transitional cytostructural characteristics between ductular cells and hepatocytes. An electron microscopic histochemical study revealed various intensities of glucose 6-phosphatase activity in the endoplasmic reticulum and nuclear envelope of the oval cells. The intensity of glucose 6-phosphatase activity in the oval cells was nearly proportional to their grade of morphological resemblance to the hepatocytes. The findings presented in this report indicate that the oval cells transform into hepatocytes through various transitional phases during azo dye carcinogenesis.

¹ This research was supported by Grant-in-Aid for Cancer Research 101056, and by Fundamental Scientific Research Grant 844033, from the Ministry of Education, Japan.

Received 2/20/74. Accepted 6/28/74.