GLUTATHIONE-S-TRANSFERASE ISOENZYME PATTERNS IN DIFFERENT SUBTYPES OFENZYME-ALTERED RAT-LIVER FOCI TREATED WITH THE PEROXISOME PROLIFERATOR NAFENOPIN OR WITH PHENOBARBITAL

It is known that phenobarbital (PB) and the peroxisome proliferator (P P) nafenopin (NAF) promote tumor formation by stimulating selective gr owth of different subtypes of liver foci. While PB enhanced the gamma- glutamyltranspeptidase (GGT)-positive eosinophilic-clear cell foci (EC F), NAF amplified the GGT-negative weakly basophilic foci (WBF). These findings provide the possibility of using the occurrence of these foc i subtypes as early indicators for the carcinogenic potential of PB- a nd PP-type promoters. In order to improve the methods for the discrimi nation between ECF and WBF we studied further differences in their phe notype, as determined by the expression pattern of glutathione S-trans ferase (GST) subunits. GST subunits of the alpha (Ya, Yc), mu (Yb1, Yb 2) and pi family (Yp), which compose different GST isoenzymes, were de monstrated by immunohistochemical methods. ECF were the only foci subp opulation that expressed GST subunit Yp, while this subunit was always absent in WBF and in another focus subtype, the tigroid foci (TF). Ne ither PB nor NAF changed this pattern. Thus Yp expression was rather a function of the focus type than of the promoter used. Upon PB treatme nt expression of the GST subunits Yb1 and Yb2 was frequently elevated in ECF, while Ya and Yc remained more or less unchanged. In NAF-treate d livers large WBF, however, showed diminished expression of all inves tigated GST subunits of the alpha and mu family. In conclusion, PB see ms to promote mostly ECF with elevated levels of mu and pi class GSTs, while low levels or absence of all GSTs tested may be associated with growth selection of WBF through the PP NAF.