| Identification of 6-azauridine triphosphate in L1210 cells and its possible relevance to cytotoxicity. | |
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MedLine Citation:
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PMID: 2463073 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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L1210 cells treated with 1 mM 6-azauridine (AzUrd) (concentration causing 50% inhibition of cell growth, 3 microM) continued to divide at a reduced rate for 72 h before stopping. However, a 24-h treatment was lethal to 99% of the cells, as determined by colony formation. To investigate the mechanism for this delayed cytotoxicity, the metabolism of AzUrd was studied. Cells incubated with AzUrd contained a new 254 nm-absorbing component, not found in control cells. It appeared to be 6-azauridine-5'-triphosphate, since it was the only peak in the triphosphate region of the chromatogram which contained 3H after incubation of cells with [3H]AzUrd. Incorporation of [3H]AzUrd into the acid-insoluble fraction (nucleic acids) was also detected. A role for this incorporation in the mechanism of AzUrd cytotoxicity was strongly suggested by the observation that cordycepin (0.01 mM) partially protected cells from the lethality of AzUrd, presumably by preventing its incorporation into RNA. The previously known inhibition of pyrimidine de novo synthesis by AzUrd was confirmed by a decrease in the intracellular contents of UTP and CTP in AzUrd-treated cells. Therefore, we propose that the inhibition of pyrimidine de novo synthesis and the incorporation into nucleic acid(s) may act in concert to produce the cytotoxic effects of AzUrd. |
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Authors:
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L L Wotring; L B Townsend |
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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: Cancer research Volume: 49 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1989 Jan |
Date Detail:
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Created Date: 1989-02-22 Completed Date: 1989-02-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 289-94 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Azauridine / analogs & derivatives*, analysis, pharmacology Cell Survival DNA, Neoplasm / drug effects Deoxyadenosines / pharmacology Hydrogen-Ion Concentration Leukemia L1210 / metabolism, pathology* Mice Nucleotides / metabolism RNA, Neoplasm / drug effects Uracil Nucleotides / analysis* Uridine Triphosphate / analogs & derivatives, analysis* |
| Chemical | |
Reg. No./Substance:
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0/DNA, Neoplasm; 0/Deoxyadenosines; 0/Nucleotides; 0/RNA, Neoplasm; 0/Uracil Nucleotides; 54-25-1/Azauridine; 6198-30-7/6-azauridine 5'-triphosphate; 63-39-8/Uridine Triphosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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