Enzyme‐altered Liver Cell Foci in Woodchucks Infected with Woodchuck Hepatitis Virus

The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)‐positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV‐negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma‐glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose‐6‐phosphatase enzyme activity compared to non‐neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV‐infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.