Changes in molecular forms of rat hepatic glutathione S-transferase during chemical hepatocarcinogenesis

Abstract

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.