Biphasic early changes in rat liver γ-glutamyl transpeptidase in response to aflatoxin B1

Abstract

The earliest changes in .gamma.-glutamyl transpeptidase (GGT) in response to administration of the hepatocarcinogen aflatoxin B1 (AFB1) were studied. Male Fischer 344 rats were either fed a diet containing 4 p.p.m., or received a single i.p. injection (0.72 or 1.73 mg/kg) of AFB1. GGT levels were determined histochemically and by quantitative fluorimetric assay. In livers of animals receiving 4 p.p.m. AGB1, GGT activity showed a biphasic response during a 15-wk period. During the first 4 wk the increasing activity was localized predominantly in the bile duct epithelial cells and some periportal hepatocytes. At 4 wk the first foci of GGT-positive hepatocytes, characteristic of the very early carcinogenic changes, began to appear. As feeding continued, there was an overall temporary decrease in GGT, during which time biliary hyperplasia regressed but the number of foci gradually increased. The 2nd phase of increased activity corresponded to increase in size and number of foci, so that by 15 wk most of GGT was present in hepatocytes. Single injections of AFB1 produced dose-dependent increases in GGT which bore a linear relationship to biliary hyperplasia.