amanitins and Glioma

The hormone-responsive enzymes tyrosine aminotransferase and glycerol-3-phosphate dehydrogenase were studied with respect to current models of the mechanism of glucocorticoid/cAMP interaction during the induction of enzyme activity in responsive cell hybrids between rat C6 glioma cells and rat FU5AH hepatoma cells. The results of experiments involving protein and mRNA synthesis inhibitors, sequential addition of inducers, and the assay of cyclic-AMP-dependent protein kinase could not be adequately explained by any one model of inducer interaction. Comparison of the hybrid clones revealed the presence of factors that may modify induction but that are not essential for synergistic induction.

Topics: Amanitins; Animals; Bucladesine; Carcinoma, Hepatocellular; Cycloheximide; Drug Synergism; Enzyme Induction; Glioma; Glycerolphosphate Dehydrogenase; Hybrid Cells; Hydrocortisone; Kinetics; Liver Neoplasms; Rats; Tyrosine Transaminase

In an effort to determine the factors that stimulate myelin synthesis, we investigated the mechanism by which dibutyryl cyclic AMP induces the activity of the myelin enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP; EC 3.1.4.37), in C6 glioma cells. Immunotitration experiments and measurements of the accumulation of [35S]methionine-labeled CNP showed that dibutyryl cyclic AMP increased the amount of CNP in the cells but not the catalytic activity per molecule of the enzyme. Moreover, inhibition of protein synthesis with cycloheximide abolished induction of enzyme activity. Dibutyryl cyclic AMP doubled the rate of CNP synthesis but had no effect on the half-life of the enzyme (approximately 33 h). The induction was partially blocked by the inhibitors of mRNA synthesis, cordycepin or alpha-amanitin. Thus, cyclic AMP induces the synthesis of CNP.

Topics: 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; 2',3'-Cyclic-Nucleotide Phosphodiesterases; Amanitins; Animals; Bucladesine; Cell Line; Cycloheximide; Deoxyadenosines; Enzyme Induction; Glioma; Immunosorbent Techniques; Kinetics; Myelin Sheath; Phosphoric Diester Hydrolases; Rats; RNA, Messenger

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenylyl Cyclases; Amanitins; Animals; Cell Line; Cyclic AMP; Dexamethasone; Glioma; Isoproterenol; Kinetics; Nucleoproteins; Phosphorylation; Protein Kinases; Rats; Receptors, Adrenergic, beta; RNA Polymerase II; Vinblastine

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Amanitins; Animals; Cell Line; Cell Nucleus; Cyclic AMP; Dactinomycin; DNA-Directed RNA Polymerases; Enzyme Induction; Glioma; Isoproterenol; Kinetics; Nerve Growth Factors; Protein Kinases; Rats; RNA Polymerase II

Nuclear RNA polymerase activity was studied in homotransplanted rat glial tumors where the primary tumor was produced by transplacental injection of ethylnitrosourea. Alpha amanitin, cycloheximide, and rifampicin were tested as inhibitors of this activity. Alpha amanitin significantly inhibited RNA polymerase activity in all tumors. This indicated that the major nuclear RNA polymerase activity seen in vitro in the tumor nuclei was RNA polymerase II. This is similar to the activity seen in normal glial nuclei. Cycloheximide and rifampicin which have no effect on RNA polymerase activity in normal glial nuclei inhibited about 20% of the polymerase activity in three of the tumors. The size and multiplicity of the nucleoli in these tumor cells suggests that RNA polymerase I could account for the activity which is inhibited by cycloheximide.

Topics: Amanitins; Animals; Autoradiography; Brain Neoplasms; Cell Nucleolus; Cell Nucleus; Cycloheximide; DNA-Directed RNA Polymerases; DNA, Neoplasm; Endoplasmic Reticulum; Ethylnitrosourea; Fibrosarcoma; Glioma; Guanosine Triphosphate; Neoplasm Transplantation; Neoplasms, Experimental; Neurofibroma; Rats; Rifampin; Transplantation, Homologous