Mechanism of bleomycin sensitivity on Escherichia coli and its possible implication on cancer chemotherapy.
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Biomedical subjects
Publications and source records attributed to H Endo.
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We analyzed the effect of asparagine starvation and L-asparaginase on RNA metabolism of mouse leukemia cell lines L5178Y, whose growth is dependent on the presence of asparagine, and L5178Y-R, whose growth is independent of the presence of asparagine. The deprivation of asparagine from the medium inhibited cellular protein synthesis by 30 to 40% of the control value in L5178Y cells, but not in L5178Y-R cells, whereas L-asparaginase inhibited synthesis by more than 80% in both L5178Y and L5178Y-R cells. The decrease in protein synthesis caused by asparagine starvation in L5178Y cells was accompanied by a decrease in ribosomal RNA synthesis. The synthesis of rRNA was also markedly blocked when L5178Y and L5178Y-R cells were exposed to L-asparaginase. The rate of synthesis of pulse-labeled RNA decreased significantly in the cells treated with L-asparaginase, and smaller pieces of polyadenylate containing pulse-labeled RNA (presumptive messenger RNA) appeared among monosomes and polysomes. However, the rate of messenger RNA synthesis was constant during asparagine starvation, and a marked accumulation of monosome was observed.
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Spinal ganglia from a patient who died on the 6th day of varicella infection were examined by immunofluorescence and electron microscopy, and were compared with spinal ganglia from a patient dying on the 17th day of herpes zoster infection. In herpes zoster, typical intranuclear inclusion bodies were found in neurons, satellite cells and fibroblast-like cells of the ganglia, which contained numerous naked virus particles. In varicella, few changes were found by light microscopy but viral antigen was detected in a few neurons and satellite cells by immunofluorescence. Electron microscopy revealed scattered virus particles near the nuclear membrane of a neuron, satellite cells and capsular cells and enveloped particles in the cytoplasm of satellite cells. The particles in the nuclei were mostly naked virions with specific crescent-like inner-nuclear structure; those in the cytoplasm had complete and incomplete envelopes and showed pleomorphism. A "virus-like" intranuclear filament found in mononuclear cells in herpes zoster and a "plexiform vermicellar array" found in the nuclei of neurons in varicella are at present considered to be non-specific nuclear changes caused probably by viral infections.
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Cytochalasin-B was found to inhibit the transport of uridine, but not leucine, in cultured fibroblastic mammalian cells. The inhibition of cellular protein synthesis by 5-fluorouracil is also lessened by the addition of Cytochalasin-B to the culture.
Synergistic effects of sulfur-containing purines and related ribonucleosides (6-thioinosine, 6-thioguanine, 6-thiocyanatopurine, 6-methylthioinosine, 6-thiocyanatoguanine, 6-thiocyanatoguanosine, 6-phenacylthioinosine, 6-nitrobenzlythioinosine, 6-(p-chlorobenzyl)thioinosine, 6-(p-nitrobenzyl)thioguanosine, 6-benzylthioinosine, 6-ethylthioinosine, 6-benzylthioguanine, 6-benzylthiopurine, 6-methylthiopurine, and 6-thiocyanatoinosine) and chlorine-containing purine and its ribonucleoside, (6-chloropuine and 6-chloropurine riboside), in combination with the polyene antibiotic, Amphotericin-B, on cell survival and synthesis of DNA were examined in mouse leukemia L5178Y cells. 6-Methylthioinosine, 6-thiocyanatopurine, 6-thiocyanatoinsoine, 6-methylthiopurine, and 6-thiocyanatoguanine (or -guanosine) among sulfur-containing compounds were strongly potentiated by Amphotericin-B, and 6-chloropurine riboside, which is electronically analogous to methylthioinosine, was also enhanced by the polyene. Thiocyanoto or methylthio group at position 6 of the purine ring seems to be important for the polyene-mediated potentiation. 6-Methylthioinosine alone had much greater effect on DNA synthesis of HeLa cells than on L5178Y cells, and Amphotericin-B failed to potentiate the action of 6-methylthioinosine in HeLa cells.
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