A new nucleosomal protein in normal liver related to the cytoplasmic polypeptide target of a carcinogen.

Normal adult rat liver contains a nucleosomal protein that is related to the principal target polypeptide of a carcinogen in cytoplasm. Normal rat liver was found previously to contain a 14 000-dalton polypeptide that is the principal cytosolic target of the carcinogen, N-2-fluorenylacetamide (2-acetylaminofluorene; FAA), early during hepatocarcinogenesis. Elevated levels of immunohistochemically detectable target polypeptide in cytoplasm are associated with normal mitosis and carcinogen-induced hyperplasias in adult hepatocytes. A putatively related 17 500-dalton polypeptide was shown to be tightly bound to chromatin of normal liver nuclei. We report here that purified nucleosomes from normal rat liver contain the bound 17 500-dalton protein. Nuclei were digested with micrococcal nuclease, and the resultant nucleosomes were resolved into size classes by density gradient sedimentation. The monomers, dimers, and trimers of nucleosomes possessed bound 17 500-dalton polypeptide, as determined by SDS gel electrophoresis followed by immunoelectroblot analyses. Alterations in the levels of the two polypeptides were shown previously to occur during liver carcinogenesis by FAA and 3'-methyl-4-dimethylaminoazobenzene. The findings support the possibility that the 17 500-dalton polypeptide may function normally in a role related to the replication or expression of the hepatic genome, and may be connected with changes in hepatic genic activity brought about by the carcinogens.