Gamma‐glutamyl Transferase as Oncofetal Marker of Experimental Hepatocarcinogenesis in the Rat

Abstract

γ‐Glutamyl transferase (γ‐GTase) is abundant in the fetal and neonatal rat liver, but almost completely disappears in the normal adult rat liver. Aflatoxin B1 (AFB1) was used in several hepatocarcinogenic models in the rat. The hepatocarcinogenesis was divided in early, preneoplastic and neoplastic phases during which liver histological changes were studied in correlation with histochemical analysis of γ‐GTase.Five types of hepatocyte populations were encountered: original hepatocytes, small newly formed hepatocytes and transitional cells, early liver cell regenerative areas, late liver cell foci and nodules and evidently malignant liver cells. A very marked γ‐GTase activity always resurged reversibly in every area of proliferating newly formed hepatocytes and transitional cells and in every early regenerative area, but it reappeared irreversibly in every late appearing focus and nodule and in every hepatocellular carcinoma. The whole remaining parenchyma (original hepatocytes) showed no γ‐GTase activity, as in the normal adult rat liver. The resurgence of γ‐GTase in these subsequent cell populations, including the malignant hepatocytes, emphasizes that the development of the latter implicates the reacquiring of some embryonal biochemical characteristics. Furthermore it illustrates the similar immature state of specific and focal preneoplastic and neoplastic liver cell lesions. γ‐GTase histochemically proved to be the most sensitive marker of the hepatocarcinogenic process.