IMMUNOHISTOCHEMICAL DEMONSTRATION OF C-MYC ONCOGENE PRODUCT AND GLUTATHIONE-S-TRANSFERASE (PLACENTAL FORM) IN RAT HEPATIC PRENEOPLASTIC LESIONS INDUCED BY DIETHYLNITROSAMINE AND CLOFIBRATE

The distribution of glutathione S-transferase (placental form; GST-P) and the c-myc gene product in rat hepatic preneoplastic lesions induced by diethylnitrosamine (DEN) and clofibrate was examined immunohistochemically. An in vivo medium-term assay system (4) was used to study the effects of chemical hepatocarcinogenesis. Rats initially received a single intraperitoneal dose (200 mg/kg) of DEN, and after week 2, 1% clofibrate in diet for consecutive days. The rats were subjected to partial hepatectomy at week 3 and sacrificed at weeks 8, 20 and 30. In rats that received clofibrate without initial DEN, no preneoplastic lesions developed. DEN produced GST-P-positive foci and/or nodules (foci/nodules), but these were decreased in number and the total area following the subsequent administration of clofibrate. Clofibrate even resulted in the appearance of GST-P-negative foci/nodules. Immunohistochemical studies revealed that the expression of c-myc gene product in the preneoplastic lesions induced by DEN was also decreased by consecutive administration of clofibrate. A similar decrease in c-myc gene product was shown also by radioimmunoassay of the liver extract from rats that received oral clofibrate subsequent to intraperitoneal DEN.