Immunohistochemical differentiation of γ-glutamyltranspeptidase in focal lesions and in zone I of rat liver after treatment with chemical carcinogens

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Abstract
γ-Glutamyltranspeptidase (γ-GT) is known to be increased in putative pre-neoplastic foci but also in the periportal zone I of rat liver under a variety of circumstances not directly related to carcinogenesis. To be able to distinguish between these two instances γ-GT was studied by enzyme determination in micro-dissections obtained from the two locations and by both histochemical and immunohistochemical staining in serial sections. Altered hepatic foci and alterations in zone I were produced in three models of hepatocarcinogenesis: (i) initiation by N -nitrosomorpholine and tumor promotion by phenobarbital, (ii) continuous administration of 2-acetyl-aminofluorene and (iii) continuous administration of meta-pyrikne hydrochloride. In micro-dissectionsγ-GT activity was similarly increased in focal lesions and in zone I after feeding methapyrilene. Histochemically detectable γ-GT, stained according to Rutenburg et al . (23), was observed both in zone I and in focal lesions. Focal lesions were also ATPase negative and UDP-glucuronyhransferase positive in all three models. γ-GT in focal lesions could be selectively detected by immunohistochemical staining using antibodies to the rat kidney enzyme and an indirect peroxidase reaction. These findings suggest immunochemical differences between γ-GT in focal lesions and in zone I.