Cellular distribution of glutathione S-transferase-P gene expression during rat hepatocarcinogenesis by diethylnitrosamine

We studied the evolution of glutathione S-transferase (GST)-P gene expression during hepatocarcinogenesis in rats treated with diethylnitrosamine (DEN) by the in situ hybridization method using a complementary RNA probe. The following findings were observed. Six weeks after the DEN treatment, distinct hybridization signals showing the presence of GST-P mRNA were found in the foci of vacuolized hepatocytes. Ten weeks after the DEN treatment, the signals were found in hepatocytes within hyperplastic nodules. Fourteen weeks after the DEN treatment, there were variously differentiated hepatocellular carcinomas, with well-differentiated hepatocellular carcinoma exhibiting signals as intense as hyperplastic nodules, and poorly-differentiated hepatocellular carcinoma exhibiting even more intense signals. Thus, the expression of GST-P gene transcripts was confirmed in the foci of vacuolized hepatocytes, with variation of gene expression in accordance with carcinoma cell differentiation.