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

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Abstract
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 acetylaminofluorene 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.