ABSTRACT
Purified histone H1 exerts growth inhibition of leukemia cells independent of lineage, stage, and maturation. At 200 micrograms/ml, H1 proved cytotoxic in 19 of 21 of the tested leukemia-derived cell lines and for 11 of 16 of the fresh tumor samples from leukemia patients. In all cases, normal peripheral blood mononuclear cells and bone marrow cells remained unaffected. Multicellular spheroids from the Burkitt's lymphoma cell line IM-9 were growth arrested at 500 micrograms H1/ml. The clonogenic growth of the Burkitt's lymphoma cell line Daudi was arrested at 160 micrograms H1/ml. Synthetic H1-peptides as well as peptides and proteins with biochemical properties similar to H1 had no inhibitory growth effect at equimolar concentrations. Furthermore, 250 micrograms H1 injected into a Burkitt's lymphoma (Daudi), xenotransplanted into nude mice, arrested tumor growth. As shown by electron microscopy and flow cytometry, incubation of leukemia cells with H1 resulted in severe plasma membrane damage and ultimately cytolysis. This report characterizes a 33-kd protein that binds H1 and is responsible for the cell death via destruction of the cell membrane integrity. New extranuclear functions of histones are presented.
Subject(s)
Histones/pharmacology , Leukemia, Experimental/pathology , Animals , Burkitt Lymphoma/pathology , Cell Membrane/physiology , Female , Histones/physiology , Leukemia, Experimental/physiopathology , Mice , Mice, Nude , Neoplasm Transplantation , Tumor Cells, Cultured/pathologyABSTRACT
A new method has been developed to raise antibodies against synthetic peptides. A multiple antigenic peptide system (MAP) containing a branched oligolysine was synthesized on a beaded polystyrene polyoxyethylene graft copolymer resin, which acts as a synthetic hapten carrier for use in immunization. The peptides, already attached to the carrier, can be used directly after final deprotection without any further purification steps. The utility of this peptide-carrier conjugate is highlighted by its additional application for affinity purification of antibodies generated.
