Changes in molecular forms of hepatic cytosolic
glutathione S-
transferases (GST) during rat chemical hepatocarcinogenesis were investigated. GST activities toward
1-chloro-2,4-dinitrobenzene and
1,2-dichloro-4-nitrobenzene increased with the increased area of gamma-glutamyltranspeptidase-positive foci and hyperplastic nodules induced by
diethylnitrosamine followed by
2-acetylaminofluorene plus
hepatectomy. Among
GSTs with high activities toward
1,2-dichloro-4-nitrobenzene, which were separated by carboxymethyl
Sephadex column chromatography, the activity of GST-A ( YbYb ) markedly increased with increased activity towards
1,2-dichloro-4-nitrobenzene in livers bearing foci and nodules and in isolated nodules and
hepatomas, while activities of GST-C ( YbYb ') and -D (Yb'Yb') changed little. It was demonstrated by
sodium dodecyl sulfate-
polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis that Yb as well as Ya , a subunit of
ligandin ( YaYa ) and GST-B ( YaYc ), increased in livers bearing foci and nodules, while Yc as well as Yb' changed little. A new placental GST form (GST-P), which has a subunit molecular weight of 21,500 or 26,000, according to the marker
proteins used, and neutral pls of 6.8 and 6.3, is immunologically different from any form of basic
GSTs and is very low in normal liver; also, it was markedly induced in livers bearing foci and nodules and in well-differentiated
hepatomas but not by short-term administration of drugs such as
2-acetylaminofluorene, in contrast to GST-A and
ligandin. These results indicate that GST-A and more especially GST-P could be new preneoplastic marker
enzymes for chemical hepatocarcinogenesis.