Enzymes of glutathione metabolism as biochemical markers during hepatocarcinogenesis

Abstract

Enzymes of glutathione metabolism, particularly gamma-glutamyltransferase (GGT) and glutathione S-transferase (GST), play a role in multistage hepatocarcinogenesis. The enhanced expression of these enzymes in preneoplastic altered hepatic foci, nodules, and hepatocellular carcinomas has been demonstrated after treatment with a variety of initiating and promoting agents. Glutathione is necessary for the detoxification of xenobiotics and carcinogens and for cell replication. Induction of GGT in altered hepatocytes may permit these cells to utilize extracellular glutathione to preserve their internal glutathione levels. GST induction allows glutathione utilization for the protection of the altered hepatocyte in an environment of exposure to xenobiotics, such as promoting agents. Thus, the combined effects of GGT and GST, in a toxic environment, may provide for the enhanced proliferation observed in preneoplastic hepatocytes. New clinical and research opportunities may involve the use of GGT and the placental isozyme of GST (PGST) as markers of preneoplasia and neoplasia in humans. Many factors, such as hormones, diet, and exposure to initiating and promoting agents, influence GGT and GST expression. The recent cloning of cDNAs to GGT and PGST offers opportunities for the study of factors involved in the genetic expression of these two enzymes. Coupled with the use of hepatocyte culture and transplantation, the factors involved at the molecular level in the creation of hepatocellular neoplasia may be discovered.

Possible Involvement of Oxidative Stress in Diethylnitrosamine-Induced Hepatocarcinogenesis: Chemopreventive Effect of Curcumin

“…2004). A restoration of these enzymes following curcumin supplementation reflects the regression of a proportion of the altered hepatic foci as a result of its hepatoprotective role (Hendricvh and Pitot 1987).…”

Celecoxib, a cyclooxygenase-2 inhibitor, prevents induction of liver preneoplastic lesions in rats

“…2A and C). Additionally, the chemopreventive effect of celecoxib on preneoplastic lesion development was quantified by measuring preneoplastic lesions with two markers, GGT and GST-P; both markers are considered the most sensitive for detection of altered hepatic foci induced by most chemicals [21]. In the HPT plus celecoxib group, both number and area of GGT-positive liver foci were significantly reduced by 80% (P%0.0001) and 90% (P%0.001), respectively, compared with the HPT group (Fig.…”

Cytokeratin 8/18 is a Useful Immunohistochemical Marker for Hepatocellular Proliferative Lesions in Mice

“…However, it is generally recognized that this immunohistochemical marker is not reactive for liver preneoplastic and neoplastic lesions of mice. It has been shown that gammaglutamyl transpeptidase (GGT) play a role in multistage hepatocarcinogenesis and the enhanced expression of this enzyme is observed in preneoplastic altered hepatocellular foci, hepatocellular adenomas, and hepatocellular carcinomas in rats and mice [13]. Therefore, GGT is used as a histochemical marker for these proliferative lesions in mice.…”