EXPRESSION OF PEROXISOMAL ENOYL-COA HYDRATASE 3-HYDROXYACYL-COA DEHYDROGENASE ENZYME AND ITS MESSENGER-RNA IN PEROXISOME PROLIFERATOR-INDUCED LIVER-TUMORS

We have examined ciprofibrate and dehydroepiandrosterone (DHEA)-induce d hepatic lesions for the peroxisomal beta-oxidation system enzyme per oxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (PBE) and its mRNA using SDS-polyacrylamide gel electrophoresis, antibodies and cDNA probe. All 12 neoplastic nodules and nine hepatocellular carcino mas (HCCs) that were analyzed for PBE mRNA by in situ hybridization sh owed an intense signal comparable to the adjacent non-neoplastic liver . SDS-polyacrylamide gel electrophoresis of postnuclear fractions of s ix HCC and adjacent liver tissue showed a marked increase in an 80 kDa polypeptide. Immunoblot and Northern blot analysis showed a marked in crease in PBE enzyme and PBE mRNA respectively in HCC and adjacent non -neoplastic liver tissue. In control livers (animals not treated with peroxisome proliferators), the levels of PBE enzyme and mRNA were very low or undetectable. The results of this study clearly indicate that peroxisome proliferator (PP)-induced liver lesions express peroxisomal enzymes to the same extent as adjacent liver and that these enzymes a re not useful markers for identification of PP-induced lesions.