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 induces peroxisome proliferation, at a concentration of 0.1% (w/w) in the diet, leads to the development of altered foci, neoplastic nodules and hepatocellular carcinomas (HCC) in the liver of rats between 21 and 70 weeks. These various lesions in liver were analyzed histochemically for gamma-glutamyl transpeptidase (GGT) activity. The presence of lipofuscin, a putative indicator of lipid peroxidation was evaluated by autofluorescence. All the altered foci, neoplastic nodules and HCC were consistently negative for GGT, and had small amounts of lipofuscin contrasted to large deposits of this pigment in the surrounding normal liver. These results indicate that GGT is not a phenotypic marker in Wy-14,643 induced hepatic carcinogenesis. Whether the neoplastic alterations induced in liver by other peroxisome proliferators are similarly GGT negative remains to be determined.