Decreased cytotoxicity of 1-beta-D-arabinofuranosylcytosine in 9L rat brain tumor cells pretreated with alpha-difluoromethylornithine in vitro. 1983

S M Oredsson, and J W Gray, and D F Deen, and L J Marton

The effect of pretreating 9L rat brain tumor cells in vitro with 10 mM alpha-difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase, on the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated using a colony-forming assay. DFMO-mediated polyamine depletion significantly decreased the cytotoxicity of ara-C. The addition of putrescine to DFMO-pretreated cells replenishes intracellular polyamine levels and prevents the decrease in ara-C cytotoxicity. Flow cytometric analysis showed that cells treated with ara-C alone entered S phase semisynchronously within 8 hr after the end of treatment. This phenomenon was virtually eliminated by DFMO pretreatment. Addition of putrescine to DFMO-pretreated cells before treatment with ara-C prevented this DFMO-induced cell cycle kinetic effect.

UI MeSH Term Description Entries
D009952 Ornithine An amino acid produced in the urea cycle by the splitting off of urea from arginine. 2,5-Diaminopentanoic Acid,Ornithine Dihydrochloride, (L)-Isomer,Ornithine Hydrochloride, (D)-Isomer,Ornithine Hydrochloride, (DL)-Isomer,Ornithine Hydrochloride, (L)-Isomer,Ornithine Monoacetate, (L)-Isomer,Ornithine Monohydrobromide, (L)-Isomer,Ornithine Monohydrochloride, (D)-Isomer,Ornithine Monohydrochloride, (DL)-Isomer,Ornithine Phosphate (1:1), (L)-Isomer,Ornithine Sulfate (1:1), (L)-Isomer,Ornithine, (D)-Isomer,Ornithine, (DL)-Isomer,Ornithine, (L)-Isomer,2,5 Diaminopentanoic Acid
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003561 Cytarabine A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472) Ara-C,Arabinofuranosylcytosine,Arabinosylcytosine,Cytosine Arabinoside,Aracytidine,Aracytine,Cytarabine Hydrochloride,Cytonal,Cytosar,Cytosar-U,beta-Ara C,Ara C,Arabinoside, Cytosine,Cytosar U,beta Ara C
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D000518 Eflornithine An inhibitor of ORNITHINE DECARBOXYLASE, the rate limiting enzyme of the polyamine biosynthetic pathway. Difluoromethylornithine,alpha-Difluoromethylornithine,DL-alpha-Difluoromethylornithine,Eflornithine Hydrochloride,Eflornithine Monohydrochloride, Monohydrate,MDL-71,782 A,Ornidyl,RMI 71782,Vaniqa,alpha-Difluoromethyl Ornithine,DL alpha Difluoromethylornithine,MDL 71,782 A,MDL71,782 A,Ornithine, alpha-Difluoromethyl,alpha Difluoromethyl Ornithine,alpha Difluoromethylornithine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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