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

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.