Pi-class glutathione transferase expression and function in mouse neoplasia

The glutathione transferases (GSTs) catalyze the glutathione conjugation re action with electrophilic compounds biotransformed from xenobiotics. Cytoso lic GST forms are grouped into four classes: Alpha, Mu, Pi and Theta. In th is article, we review recent findings of GST expression in mouse hepatic pr eneoplastic lesions and the function of Pi-class forms in cancer cells. The majority of mouse liver foci could be detected as Pi-class-positive popula tions in females, while those in males exhibited decreased expression relat ive to the background. However, absolute Pi-class mRNA or protein levels in the lesions were almost the same in both males and females. Of two Pi-clas s genes (p-l and p-2), the p-l gene was found to be dominantly expressed wi th a suggested contribution of its TPA-responsive element (TRE). In a separ ate model, the influence of a combination of lentinan and cisplatin on the growth and GST content of the colon-26 tumor was investigated. Tumor weight s were lower in the combination group than in the cisplatin alone group, an d lentinan repressed GST expression. Furthermore, two GST inhibitors, benas tatin A and ethacrynic acid, induced apoptosis in colon-26 cells. These fin dings are of potential importance with regard to overcoming the anti-cancer drug resistance related to GSTs.