HISTOCHEMICAL DEMONSTRATION OF INCREASED ACTIVITY OF γ-GLUTAMYL TRANSPEPTIDASE IN RAT LIVER DURING HEPATOCARCINOGENESIS

Abstract

Histochemical demonstration of .gamma.-glutamyl transpeptidase (.gamma.-GTP) during chemically induced hepatocarcinogenesis in rats was studied. The carcinogens employed were N-OH-FAA (N-hydroxy derivative of N-2-fluorenylacetamide), and aflatoxin B1. In control rats, activity of .gamma.-GTP was demonstrated in bile duct cells and occasionally along the bile canaliculi, but not in hepatocytes. Proliferating bile duct cells including so-called oval cells and cholangiocarcinoma cells, and hepatocytes of hyperplastic areas and nodules and hepatocellular carcinoma induced by N-OH-FAA, with or without aflatoxin B1, revealed positive activity of .gamma.-GTP, histochemically. Only focal demonstration of .gamma.-GTP activity in hepatocytes was observed in association with a mild hyperplastic change in rats treated with aflatoxin B1 alone. The elevation of .gamma.-GTP activity in serum and liver tissue with the appearance of the fetal isoenzyme pattern was also demonstrated biochemically and correlated with the histochemical appearance of .gamma.-GTP activity in liver tissue from the early phase of hepatobiliary carcinogenesis. These results seem to demonstrate carcinoembryonic nature of induced .GAMMA.-GTP in the development of cholangiocellular and hepatocellular carcinomas.