streptovaricin-c and Cell-Transformation--Neoplastic

n-Pentyl ether of damavaricin Fc (n-pentyl DvFc) preferentially killed human T-cell lymphotropic virus type I (HTLV-I)-transformed cell lines. The mechanism of action of the drug was investigated using MT-4 cells. Cytotoxic action was diminished by the removal of n-pentyl DvFc from the culture or by the addition of sulfhydryl compounds such as 2-mercaptoethanol and dithiothreitol. The killing activity of n-pentyl DvFc was also diminished by membrane-acting agents including quinidine and diphenylhydantoin. Influx and subsequent efflux of Ca2+ were observed when either HTLV-I infected (MT-4 cells) or uninfected cells were treated with n-pentyl DvFc. An efflux of K+ was observed in HTLV-I infected MT-4 cells immediately after the exposure of the cells to n-pentyl DvFc. The K+ efflux, however, was not observed in the uninfected T cells. n-Pentyl DvFc seems to act primarily on the cell surface of MT-4 cells, leading to the perturbation of membrane function. The restoration of cell growth, however, is critically dependent on the presence of dithiothreitol and 2-mercaptoethanol, implying a role for a free sulfhydryl group in the killing activity.

Topics: Anti-Bacterial Agents; Antiviral Agents; Calcium; Cell Line, Transformed; Cell Membrane; Cell Membrane Permeability; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Dithiothreitol; DNA; Human T-lymphotropic virus 1; Humans; Leukemia, T-Cell; Mercaptoethanol; Phenytoin; Potassium; Quinidine; Streptovaricin; T-Lymphocytes

Topics: Adenocarcinoma; Administration, Oral; Animals; Cell Transformation, Neoplastic; Female; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Streptovaricin

Topics: Amantadine; Animals; Antiviral Agents; Azauridine; Cell Transformation, Neoplastic; Cytarabine; Deoxyuridine; DNA-Directed RNA Polymerases; Herpesviridae Infections; Humans; Idoxuridine; Interferons; Protein Biosynthesis; Rifampin; Rifamycins; RNA-Directed DNA Polymerase; RNA, Viral; Streptovaricin; Structure-Activity Relationship; Thiosemicarbazones; Transcription, Genetic; Vaccinia virus

Rifamycin antibiotics, which inhibit RNA-directed DNA polymerase of Rauscher leuckemia virus, prevent the leukemogenic activity of the virus, and the effect of leukemogenesis correlates with the magnitude of inhibition of the purified enzyme. This inhibition of enzyme activity by rifamycin SV derivatives is due to a relatively tight binding between the enzymes and the inhibitors, yet the binding can be reversed by nonionic detergent. The results of this study suggest that RNA-directed DNA polymerase is essential for induction of leukemia by exogenous virus and correlate with the previous observation that the same derivatives block viral transformation in vitro.

Topics: Animals; Binding Sites; Cell Transformation, Neoplastic; Chromatography, DEAE-Cellulose; Female; Injections, Intravenous; Leukemia, Experimental; Male; Mice; Rauscher Virus; Reverse Transcriptase Inhibitors; Rifamycins; RNA-Directed DNA Polymerase; Splenomegaly; Streptovaricin; Surface-Active Agents

Topics: Animals; Antibiotics, Antineoplastic; Cell Division; Cell Line; Cell Transformation, Neoplastic; Chemical Phenomena; Chemistry; Culture Techniques; DNA Nucleotidyltransferases; Drug Synergism; Interferons; Leukemia Virus, Murine; Mice; Streptovaricin; Time Factors

Topics: Animals; Antibiotics, Antineoplastic; Cell Transformation, Neoplastic; Erythropoiesis; Leukemia, Experimental; Lymphoma; Mice; Organ Size; Rauscher Virus; Splenomegaly; Streptovaricin; Time Factors