Immunohistochemically demonstrated glucose-6-phosphate dehydrogenase, γ-glutamyl transpeptidase, ornithine decarboxylase and glutathione S-transferase enzymes: absence of direct correlation with cell proliferation in rat liver putative preneoplastic lesions

Abstract

Comparison of binding of specific antibodies to glu-cose-6-phosphate dehydrogenase (G6PD), γ-glutamyl trans-peptidase (GT), ornithine decarboxylase (ODQ and the glutathione S-transferase B and P forms (GST-B, P) was made in putative pre-neoplastic lesions during their induction and subsequent development using the Solt-Farber model. The earliest focal hepatocellular lesions were evident as single, or small groups of GST-P-positive hepatocytes in tissue taken at partial hepatectomy 3 weeks after initial application of di-ethylnitrosamine (DEN). With the onset of proliferation and increase in size the majority of the lesions expressed elevated levels of all of the enzyme proteins investigated with a correlation between strength of binding and morphology being apparent. While [ ³ H]thymidine incorporation was limited during the period of acetylaminofluorene administration, to the hepatocytes demonstrating altered enzyme phenotype no direct link between proliferation rate within individual foci and level of G6PD expression could be discerned. Similarly, the elevated level of labelling characteristic of persisting nodular lesions at later stages also did not correlate with degree of G6PD alteration in individual cells. The results indicate that while changed enzyme phenotype appears as an ordered pattern suggestive of physiological adaptive nature, the degree of alteration is not directly related to proliferation kinetics under the rapid induction conditions characteristic of the Solt-Farber model.