| Implications for a reduced DNA-elongation rate in polyamine-depleted cells. | |
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MedLine Citation:
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PMID: 2115438 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Treatment of Ehrlich ascites tumor cells with 2-difluoromethylornithine (F2MeOrn), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, resulted in depleted putrescine and spermidine content, and reduced growth rate. We have previously shown that adenine ribonucleotide levels are substantially increased in these polyamine-depleted cells. The present paper addresses the question whether the elevated ATP pool is accompanied by a concomitant increase in the dATP pool. If this is the case, the observed growth inhibition could be explained by the well-known dATP-mediated feedback inhibition of ribonucleotide reductase. We found that dNTP pools were not unbalanced and that dNTP synthesis was not arrested in polyamine-depleted cells. Moreover, the dNTP content and the activity of ribonucleotide reductase (CDP reduction) and thymidylate synthase, remained elevated despite the fact that the cells were inhibited in their growth by F2MeOrn treatment. Incorporation of a radiolabeled precursor into DNA was initially lower in F2MeOrn-treated. cells than in control cells. However, while incorporation of a radiolabeled precursor into DNA decreased markedly in plateau-phase control cells, it remained at a higher level in cells inhibited in growth by polyamine depletion. This discrepancy may be explained by the fact that polyamine-depleted cells accumulated in the S phase, and that they had an increased content of acid-soluble radiolabeled DNA precursor. Our data indicate that polyamine depletion adversely affects the DNA synthetic machinery by reducing the rate of elongation. |
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Authors:
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S M Oredsson; B Nicander; O Heby |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of biochemistry / FEBS Volume: 190 ISSN: 0014-2956 ISO Abbreviation: Eur. J. Biochem. Publication Date: 1990 Jul |
Date Detail:
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Created Date: 1990-08-24 Completed Date: 1990-08-24 Revised Date: 2007-07-23 |
Medline Journal Info:
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Nlm Unique ID: 0107600 Medline TA: Eur J Biochem Country: GERMANY, WEST |
Other Details:
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Languages: eng Pagination: 483-9 Citation Subset: IM |
Affiliation:
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Department of Zoo Physiology, University of Lund, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carcinoma, Ehrlich Tumor / metabolism* Cell Cycle / drug effects Cell Division / drug effects DNA Replication / drug effects DNA, Neoplasm / biosynthesis*, drug effects Deoxyribonucleotides / metabolism* Eflornithine / pharmacology* Kinetics Mice Putrescine / metabolism* Spermidine / metabolism* Thymidylate Synthase / metabolism* Tumor Cells, Cultured / cytology, drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA, Neoplasm; 0/Deoxyribonucleotides; 110-60-1/Putrescine; 124-20-9/Spermidine; 70052-12-9/Eflornithine; EC 2.1.1.45/Thymidylate Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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