Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study is to examine effects of methylnitrosourea (MNU) on electron microscopic visualization of acridine orange (AO) binding to DNA in mouse lymphoma L-1210 cells and to demonstrate alteration of the euchromatin/heterochromatin ratio by morphometry. [3H] uridine uptake into RNA molecule is inhibited and percentage of AO positive cells is decreased to approximately 20% of that of the untreated control cells by treatment of the lymphoma cells with MNU. When the MNU-treated cells are cultured in the presence of 3-amino-benzamide, a specific inhibitor of poly(ADP-ribose) synthetase, the depression in RNA synthesis is prevented, and percentage of AO positive cells as well as numbers of AO chromatin interaction products per single cell nucleus are also completely recovered as compared to those in the untreated cells. In the MNU-treated cells the decreased number of AO positive cells coincides with a reduced [3H] uridine uptake as well as with a lowered euchromatin/heterochromatin ratio. The results suggest that visualization of AO chromatin interaction products in the proliferating cells is related not only to RNA synthesis in the cells, but also to the euchromatin/heterochromatin ratio.
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PMID:Effects of methylnitrosourea on visualization of acridine orange binding to DNA in mouse lymphoma L-1210 cells. 309 May 24

Predictive capacity and clinical usefulness of the short term predictive assay (STPA) in the inductive treatment of patients with acute nonlymphoblastic leukemia (ANLL) was studied. Inductive treatment consisted of daunorubicin, arabinoside C and 6-thioguanine (TAD regimen). Leukemic cells of 20 previously untreated patients with ANLL were incubated in vitro with two doses of daunorubicin (1 microgram/ml and 10 micrograms/ml), arabinoside C (10 micrograms/ml and 100 micrograms/ml) and 6-thioguanine (10 micrograms/ml and 100 micrograms/ml). The 3H-thymidine as well as 3H-uridine uptake was measured in the treated and untreated cells. The highest predictive presence of the in vivo drug-sensitive disease was adequately reflected by the level of 3H-uridine incorporation suppression 30% of control value in the case of daunorubicin (concentration: 10 micrograms/ml) and 80% in the case of 6-thioguanine (concentration: 100 micrograms/ml). In the case of arabinoside C (concentration: 10 micrograms/ml) the limit of 3H-thymidine uptake depression was 20% of control value. It was rather difficult to define the indicative degree of precursors incorporation inhibition for prediction of the drug-resistant disease, because of low number of patients primary resistant to TAD regimen. No correlation was found between the degree of the pre-treatment DNA synthesis rates and the precursors uptake inhibition by the tested drugs.
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PMID:The value of the short term predictive assay in the inductive treatment of patients with acute nonlymphoblastic leukemia. 380 27

Gordon, Irving (University of Southern California, Los Angeles), Sara S. Chenault, Douglas Stevenson, and Jean D. Acton. Effect of interferon on polymerization of single-stranded and double-stranded mengovirus ribonucleic acid. J. Bacteriol. 91:1230-1238. 1966.-The effect of interferon on actinomycin-resistant mengovirus ribonucleic acid (RNA) replication in L cells was investigated to determine whether defective or partially polymerized RNA products were made and whether synthesis of any specific class of virus RNA was prevented. RNA labeled with uridine-C(14) was extracted in hot and cold phenol and analyzed by zonal sucrose density centrifugation. Both single- and double-stranded infectious RNA peaks were identified. Interferon treatment caused almost complete depression of uridine-C(14) incorporation throughout linear sucrose gradients except in the 4S region, and no infectivity was detectable in any fraction. These inhibitory effects are attributable to the action of interferon, because they were reversed when cultures were treated with actinomycin D simultaneously with interferon. The results, with those of other investigators, indicate that the step at which interferon interrupts virus multiplication is between the events immediately after uncoating and the formation of template "minus" strands; under the conditions of our experiments, no partially polymerized virus RNA products were made.
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PMID:Effect of interferon on polymerization of single-stranded and double-stranded mengovirus ribonucleic acid. 428 47

9-beta-d-Arabinofuranosyladenine (Ara-A) effectively inhibited the production of infectious vesicular stomatitis virus (VSV) in MDBK cells. Furthermore, inhibition was shown to begin as early as the first 3 hr of infection. Studies employing (3)H-l-leucine indicated that Ara-A did not affect protein synthesis in uninfected cells, although it did cause a marked stimulation of protein synthesis in VSV-infected cells during the log phase of the growth cycle. Puromycin, an inhibitor of protein synthesis, was a more effective viral inhibitor than Ara-A. However, the combination of Ara-A and puromycin was less effective than puromycin alone except when present for long time periods. Short-term labeling experiments with (3)H-uridine demonstrated that Ara-A depressed ribonucleic acid (RNA) synthesis in uninfected cells, whereas periods of stimulation and depression of radioisotope incorporation occurred in infected cells. The results support the notion that Ara-A is incorporated into RNA early during viral replication.
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PMID:Inhibition of vesicular stomatitis virus replication by 9-beta-D-arabinofuranosyladenine. 436 72

Isoproterenol stimulates cell proliferation in mouse salivary glands. Prior to the stimulation of DNA synthesis, (3)H-uridine incorporation into RNA is decreased. This decreased incorporation results from a depression of uridylate kinase activity.
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PMID:Uridylate kinase activity: effect of isoproterenol. 567 33

Following the administration of D-galactosamine the utilization of [2-14C] orotic acid for the synthesis of the cytidine components of the acid-soluble extract and liver RNA cytosine is markedly decreased. The depression of the specific activity of the cytidine components takes place after application of low doses of the drug which do not interfere with the specific activity of the uridine components of the acid-soluble extract or of liver RNA uracil. Simultaneously the administration of [U-14C]cytidine paralleled by its enhanced liver uptake. The total amount of uridine as well as cytidine components of the acid-soluble extract following the administration of D-galactosamine increases; however, the molar ratio of both pyrimidines does not change. The alterations of the cytidine metabolism after the administration of the drug are accompanied by the increased level of microsomal cytochrome P-450.
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PMID:Biosynthesis of cytidine nucleotides in rat liver after administration of D-galactosamine. 616 66

Hyperthermic treatment of HeLa cells at 42 degrees C for 60 min depressed the specific activity of these cells when incubated with 3H-uridine both during and post heating compared to cells maintained at 37 degrees C. These changes were unlikely to arise from increased leakage from the cells and may partially be attributed to membrane damage influencing facilitated diffusion. Diffusion kinetic data for incorporation of the radiolabel into the T.C.A. soluble and T.C.A. insoluble fractions of HeLa cells indicated that a significant depression of Vmax and a significant elevation of Km for incorporation of 3H UdR into RNA may possibly result from an isotope dilution effect attributed to degrading pre-ribosomal RNA under the effect of hyperthermia.
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PMID:Diffusion kinetics of tritiated uridine into HeLa cells previously exposed to hyperthermia. 616 60

Three antiviral hetarylhydrazones showed a depression of 3H-uridine incorporation into RNA of FL cells as a consequence of inhibition of uridine transport into the cells. By eliminating the action of the compounds on transport processes with the prelabelling method, only one compound showed a nearly 50% reduction of cellular RNA synthesis during the whole incubation period, whereas the other two compounds had no influence during the first 6 hr. Under prelabelling conditions all three compounds completely inhibited the synthesis of Mengo virus RNA. One compound did not affect cellular DNA synthesis, but presumably depressed thymidine transport into the cells.
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PMID:Mechanism of action of antiviral hetarylhydrazones in vitro. 616 84

When mouse lymphoma cells (L-1210) are treated with methylnitrosourea, a DNA-damaging agent, polyadenosine diphosphoribose (poly(ADP-ribose)) synthetase activity increases 5-8-fold in 2-3 h, while RNA polymerase activity remains constant for an initial 2 h and then gradually decreases to 25-30% of the control level in 5 h. Both alpha-amanitin-sensitive and -resistant RNA polymerase activities are depressed to the same degree by the treatment with methylnitrosourea. The depression in RNA synthesis is virtually prevented when the treated cells are cultured in the presence of 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) synthetase. Analyses of the RNA extracted from the cells labeled with [3H]uridine by agarose gel electrophoresis and by poly(U)-Sepharose column chromatography show that the contents of ribosomal precursor RNA and poly(A)-containing RNA are both low in the methylnitrosourea-treated cells as compared with those in the untreated cells and that the reduction in the contents of these kinds of RNA is almost completely prevented by the addition of 3-aminobenzamide to the culture medium. These results suggest that the enhancement of poly(ADP-ribosyl)ation causes the decrease in both synthesis of ribosomal RNA and messenger RNA.
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PMID:Participation of poly(ADP-ribosyl)ation in the depression of RNA synthesis caused by treatment of mouse lymphoma cells with methylnitrosourea. 617 37

Doses of N-(phosphonacetyl)-L-aspartic acid (PALA) lower than those required for therapeutic activity against the spontaneous murine breast tumor (BALB/c X DBA/8 F1) were found to produce significant depression in uridine triphosphate pools in the tumor. Using such low, nontherapeutic, but biochemically active doses of PALA in combination with 5-fluorouracil (FUra(, it was possible to maintain the dose of FUra at its full maximum tolerated single agent dose. In comparison with the maximum tolerated dose of FUra alone, the combination of FUra plus low-dose PALA produced a significant increase in the level of tumor FUra-containing RNA, only a slight increase in intestinal FUra-containing RNA, and no increase in bone marrow FUra-containing RNA. These biochemical results correlated with the therapeutic findings of significantly increased antitumor activity without an increase in host toxicity. A review of currently reported PALA plus FUra clinical protocols reveals that the experimental parameters which have produced successful therapeutic results in the laboratory (i.e., a low-PALA:high-FUra dosage ratio) have not yet been translated into clinical trial. Final judgment on the clinical efficacy of PALA:FUra combinations must await the results of proposed low-PALA:high-FUra clinical trials.
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PMID:Therapeutic utility of utilizing low doses of N-(phosphonacetyl)-L-aspartic acid in combination with 5-fluorouracil: a murine study with clinical relevance. 618 48


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