GAMMA-GLUTAMYLTRANSFERASE IN PUTATIVE PREMALIGNANT LIVER-CELL POPULATIONS DURING HEPATOCARCINOGENESIS

Abstract

The activity of .gamma.-glutamyltransferase, as measured quantitatively and by histochemical staining, was studied in different cell populations during the induction of liver cancer with 2-acetylaminofluorene (2-AAF) or diethylnitrosamine and compared with findings in fetal and intact and regenerating adult rat liver. The enzyme activity is 20-fold higher in 12-wk nodules than in control livers and 30-fold higher in 20-wk nodules than in controls. A similar 30-fold increase in activity relative to control is present in hepatomas, induced by 2-AAF or diethylnitrosamine, and in feal hepatocytes. The enzyme shows increases in activity in foci of early putative preneoplastic hepatocytes induced by a single dose of diethylnitrosamine and selected by low doses of 2-AAF plus partial hepatectomy. By 7 days, the foci show a 4-fold increase in enzyme activity, and by 3 wk they are 40-fold higher than in the control liver. Histochemically, the foci are strongly positive for .gamma.-glutamyltransferase, especially in the bile canaliculi. By 21 days, the ductular (oval) cells induced by 2-AAF have disappeared. When stained for enzyme activity, the foci stand out clearly against the negative background of the liver, allowing easy quantitation. It appears that .gamma.-glutamyltransferase is a useful marker for preneoplastic hepatocytes.