ABSTRACT
The in vivo antitumor effectiveness [as measured by the percentage increase in life-span (ILS%)] of 28 diacridine bis-intercalators of nucleic acids shows a highly significant correlation with their effect on phenomena associated with plasma membrane as well as a high degree of structural specificity. In contrast, the ILS% does not correlate with the uptake of these diacridines by cells, nor with the inhibition of RNA synthesis or of DNA synthesis or with the inhibition of growth of cells in culture. The possibility that the antitumor effectiveness of actinomycin D, another DNA intercalator, is associated with sites of action other than the hibition of RNA synthesis is discussed.
Subject(s)
Acridines/pharmacology , Cell Aggregation/drug effects , Cell Membrane/drug effects , Neoplasms, Experimental/drug therapy , Acridines/metabolism , Acridines/therapeutic use , Biological Transport , Cell Line , DNA/biosynthesis , Dactinomycin/pharmacology , Dactinomycin/therapeutic use , RNA/biosynthesis , Structure-Activity RelationshipSubject(s)
Acridines/pharmacology , Cell Nucleolus/metabolism , RNA/biosynthesis , Acridines/metabolism , Cell Nucleolus/drug effects , Cell Nucleus/ultrastructure , Centrifugation, Density Gradient , Depression, Chemical , HeLa Cells/drug effects , HeLa Cells/metabolism , HeLa Cells/ultrastructure , Humans , Structure-Activity RelationshipSubject(s)
Acridines/pharmacology , Escherichia coli , RNA, Bacterial/metabolism , RNA, Ribosomal/biosynthesis , RNA, Transfer/metabolism , Animals , Centrifugation, Density Gradient , Depression, Chemical , HeLa Cells/drug effects , HeLa Cells/metabolism , In Vitro Techniques , Liver/enzymology , Methylation , Rats , tRNA Methyltransferases/metabolismABSTRACT
Electron microscopy of HeLa cells exposed to spermine diacridine shows nucleolar distortions which disappear after several days despite the persistence of the metabolic changes promoted by spermine diacridine. This compound inhibits ribosomal RNA synthesis and appears to act independently of any particular phase of the cell cycle. The DNA content of the HeLa cells remains unchanged and the cell distribution is not significantly disturbed from its normal distribution in the various phases of the cell cycle. Spermine diacridine and other diacridines inhibit primarily chain initiation but also chain elongation by DNA-directed RNA polymerase of Azotobacter vinelandii.
