Stable Expression of Glutathione S-transferase P-form mRNA and TGF-α Immunohistochemical Expression are Useful Markers for Identification of Persistent Nodules from an Early Stage in Rat Hepatocarcinogenesis

Abstract

Expression of glutathione-S-transferase P-form (GST-P) mRNA revealed by in situ hybridization histochemistry was investigated in enzyme altered foci and nodules during rat hepatocarcinogenesis, using diethylnitrosamine initiation followed by 2-acetylaminofluorene promotion protocol. The majority of early foci showed uniformly high levels of GST-P mRNA, however, some lesions after completion of the promotion regimen exhibited a progressive loss of expression of GST-P mRNA. Most of the continuous and strong GST-P mRNA positive lesions were also transforming growth factor-α (TGF-α)-positive lesions, a putative potent mitogen for altered hepatocytes. Moreover, the proliferating cell nuclear antigen (PCNA) index was significantly (p<0.05) greater in the GST-P mRNA-positive nodules than that in negative ones. These results suggest that stable expression of GST-P mRNA is a very useful marker for identification of developing preneoplastic lesions during rat hepatocarcinogenesis.