Glutathione S-transferase localization in aflatoxin B1-treated rat livers

Carcinogenesis
D J HarrisonG E Neal

Abstract

Overexpression of detoxication enzymes is associated with the development of drug-resistant, preneoplastic nodules in the carcinogen-treated rat liver. The most consistent marker of preneoplasia in many experimental models is increased expression of the pi-class glutathione S-transferase (GST) YfYf. We have confirmed by immunostaining that the pi-class GST is overexpressed in aflatoxin B1-induced preneoplastic nodules and liver tumours in rats. However, pi-class GST YfYf has low activity against aflatoxin B1-8,9-epoxide, and most activity against this cytotoxic and genotoxic metabolite is associated with the alpha-class GSTs YaYa, YaYc and YcYc. We have demonstrated that there is also a consistent increase in the alpha-class GSTs in this model. It seems likely that the overexpression of the Ya and Yc subunits, rather than increased levels of the pi-class GST YfYf, is responsible for the acquisition of a drug-resistant phenotype in rat liver preneoplastic nodules and tumours induced by aflatoxin B1.

Citations

Aug 8, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Q SuP Bannasch
Apr 1, 1994·European Journal of Drug Metabolism and Pharmacokinetics·S RaisuddinP K Ray
Nov 15, 2006·Infection and Immunity·Marina HarvieAnne Camille La Flamme
Dec 1, 1991·Gut·P C HayesD J Harrison
Nov 1, 1995·Human & Experimental Toxicology·J D Hayes
Jan 1, 1992·Critical Reviews in Biochemistry and Molecular Biology·S Tsuchida, K Sato
Aug 10, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Vikash ReebyeNagy A Habib

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