Immunofluorescent analysis of γ-glutamyl transpeptidase and glutathione-s-transferase-p during the initial phase of experimental hepatocarcinogenesis

We used double-label immunofluorescence to evaluate the expression of glutathione-S-transferase-P (GST-P) and γ-glutamyl transferase (γGT) in individual liver cells in rats placed on a modified Solt-Farber hepatocarcinogenesis protocol. Four days after treatment with diethylnitrosamine (DEN), single GST-P⁺ cells were found in the centrilobular and midzonal regions. Most of these were γGT^-, but the percentage of γGT⁺ cells increased with DEN dose to a high of 32%. At later times (7-8 days) doublets and small clusters of GST-P⁺ cells predominated; all cells in each pair or cluster displayed the same phenotype (GST-P⁺ or GST-P⁺/γGT⁺). Following administration of acetylamino-fluorene and partial hepatectomy, lesions were larger and a greater percentage were GST-P⁺/γGT⁺. However, within these lesions individual cells displayed different phenotypes. These results indicate that the expression of GST-P and γGT is discordant in individual cells and small clusters soon after treatment, and suggest that different molecular events may be involved in their expression.