The absence of {gamma}glutamyl transpeptidase activity in putative preneoplastic lesions and in hepatocellular carcinomas induced in rats by the hypolipidemic peroxisome proliferator Wy-14,643

Administration of Wy-14,643, a hypolipidemic agent which inducesperoxisome proliferation, at a concentration of 0.1% (w/w) inthe diet, leads to the development of altered foci, neoplasticnodules and hepatocellular carcinomas (HCC) in the liver ofrats between 21 and 70 weeks. These various lesions in liverwere analyzed histochemically for -glutamyl transpeptidase (GGT)activity. The presence of lipofuscin, a putative indicator oflipid peroxidation was evaluated by autofluorescence. All thealtered foci, neoplastic nodules and HCC were consistently negativefor GGT, and had small amounts of lipofuscin contrasted to largedeposits of this pigment in the surrounding normal liver. Theseresults indicate that GGT is not a phenotypic marker in Wy-14,643 induced hepatic carcinogenesis. Whether the neoplastic alterationsinduced in liver by other peroxisome proliferators are similarlyGGT negative remains to be determined.