Action of 9-beta-D-arabinofuranosyl-2-fluoroadenine on RNA metabolism. 1991

P Huang, and W Plunkett
Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

The action of 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) on RNA metabolism was evaluated both in whole cells and in cell-free systems. F-ara-A was converted to its 5'-triphosphate, F-ara-ATP, in cells and then incorporated into RNA as well as DNA. F-ara-A inhibited RNA synthesis in cultured cells in a concentration-dependent manner. This inhibition was mediated mainly by F-ara-ATP. Experiments using isolated nuclei demonstrated that RNA polymerases I, II, and III accounted for 24, 73, and 3% of the total RNA synthesis activity, respectively. About 88% of the total inhibition was attributed to the suppression of RNA polymerase II activity. In cultured cells, F-ara-A was preferentially incorporated into the poly(A)+ RNA fraction. Approximately 78% of the incorporated F-ara-A monophosphate residues were located at the terminal position of the RNA chain. The incorporation of F-ara-A monophosphate into mRNA resulted in premature termination of the RNA transcript and impaired its functioning as a template for protein synthesis. The inhibitory action of F-ara-A on RNA metabolism is a unique property of this compound, differing from the action of arabinosylcytosine and arabinosyladenine.

UI MeSH Term Description Entries
D011061 Poly A A group of adenine ribonucleotides in which the phosphate residues of each adenine ribonucleotide act as bridges in forming diester linkages between the ribose moieties. Adenine Polynucleotides,Polyadenylic Acids,Poly(rA),Polynucleotides, Adenine
D002474 Cell-Free System A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166) Cellfree System,Cell Free System,Cell-Free Systems,Cellfree Systems,System, Cell-Free,System, Cellfree,Systems, Cell-Free,Systems, Cellfree
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D014176 Protein Biosynthesis The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS. Genetic Translation,Peptide Biosynthesis, Ribosomal,Protein Translation,Translation, Genetic,Protein Biosynthesis, Ribosomal,Protein Synthesis, Ribosomal,Ribosomal Peptide Biosynthesis,mRNA Translation,Biosynthesis, Protein,Biosynthesis, Ribosomal Peptide,Biosynthesis, Ribosomal Protein,Genetic Translations,Ribosomal Protein Biosynthesis,Ribosomal Protein Synthesis,Synthesis, Ribosomal Protein,Translation, Protein,Translation, mRNA,mRNA Translations
D014740 Vidarabine A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus. Adenine Arabinoside,Ara-A,Arabinofuranosyladenine,Arabinosyladenine,9-beta-Arabinofuranosyladenine,9-beta-D-Arabinofuranosyladenine,Ara A,Vira-A,alpha-Ara A,alpha-D-Arabinofuranosyladenine,beta-Ara A,9 beta Arabinofuranosyladenine,9 beta D Arabinofuranosyladenine,Arabinoside, Adenine,Vira A,ViraA,alpha Ara A,alpha D Arabinofuranosyladenine,beta Ara A

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