Focal elevation of liver microsomal epoxide hydrolase in early preneoplastic stages and its behaviour in the further course of hepatocarcinogenesis

Wolf D. Kuhlmann, R. Krischan, W. Kunz, T. M. Guenthner, F. Oesch


Institute of Nuclear Medicine (W.D.K.) and Institute of Biochemistry (R.K. and W.K.)
German Cancer Research Center, D-6900 Heidelberg
Institute of Pharmacology (T.M.G. and F.O.), University of Mainz, D-6500 Mainz, FRG
Treatment of rats with N-nitrosomorpholine (NNM) for 7 weeks led to a focal increase in liver microsomal epoxide hydrolase (EH) as early as 2 weeks after withdrawal of the carcinogen as shown by immunoperoxidase labeling. NNM treatment also leads to hyperplastic nodules and liver tumors, but much later. At the same early time point, ATPase activity was decreased in the same islands. Most of these areas already had increased ã-glutamyltranspeptidase activity. The increase in EH at this early time point was more distinct than the decrease in ATPase which has thus far been considered a suitable marker of the earliest stages in hepatocarcinogenesis. The focal increase in EH was also observed in all benign hepatomas, but not in any of the hepatocellular carcinomas investigated so far.