CHANGES IN MOLECULAR-FORMS OF RAT HEPATIC GLUTATHIONE S-TRANSFERASE DURING CHEMICAL HEPATOCARCINOGENESIS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (6) , 2698-2703
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-aetylaminofluorene plus hepatectomy. Among GST with high activities toward 1,2-dichloro-4-nitrobenzene, which were separated by carboxymethyl Sephadex column chromatography, the activity of GST-A (YbYb) markedly incresed 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 MW of 21,500 or 26,000, according to the marker proteins used, and neutral pI [isoelectric point] of 6.8 and 6.3, is immunologically different from any form of basic GST 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. GST-A and more especially GST-P could be new preneoplastic marker enzymes for chemical hepatocarcinogenesis.