Comparative study of abnormality in glycogen storing capacity and other histochemical phenotypic changes in...

A sequential comparison was made between abnormal glycogen storage and other histochemical phenotypic changes in hepatocellular precancerous lesions (altered foci and neoplastic nodules) during various stages in the process of development of cancer in rat liver. N-2-fluorenylacetamide was fed to male rats for 8 weeks and groups of rats were killed at the end of carcinogen feeding and at 12 and 24 weeks on control diet. Foci rich in glycogen storage accounted for a majority of all foci over the course of experiment, while foci devoid of glycogen storage, which were absent at the end of carcinogen feeding, gradually increased in number during maintenance. Glycogen-deficient lesions that might appear to arise from glycogen-rich lesions displayed hyperbasophilia demonstrated by toluidine blue reaction, but often lacked gamma-glutamyl transpeptidase activity. Resistance to iron accumulation was consistently shown in all precursor lesions for hepatocellular carcinoma in the siderotic liver regardless of abundance or absence of cellular glycogen. It was suggested that properties such as loss of glycogen storing capacity, hyperbasophilia, and some cellular atypicality resembling those of carcinoma cells might be essential elements for malignant progression.