Absence of gamma-glutamyltranspeptidase activity in lung metastasis in rats with hepatocellular carcinomas induced by ciprofibrate, a peroxisome proliferator

The incidence of lung metastasis in rats with hepatocellular carcinomas (HCC) induced by ciprofibrate, a peroxisome proliferator and the expression of gammaglutamyl transeptidase (GGT) in the metastatic lesions was studied. HCC were induced in 75 male F-334 rats by chronic dietary administration of ciprofibrate (0.025% w/w) for 16-22 months. The incidence of lung metastasis was 25% in rats killed between 14 and 16 months which increased to 56% in rats killed between 20 and 22 months. The lung metastases were multifocal and present in both the blood vessels and parenchyma. All the metastatic foci examined for the expression of GGT by histochemical stain were devoid of this enzyme. The results of this study clearly demonstrate the malignant behavior of ciprofibrate-induced liver tumors and the absence of GGT expression in metastatic lesions a phenotypic property that is peculiar to the primary HCC induced by several peroxisome proliferators.