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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1983-1-7
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pubmed:abstractText |
Results are described that demonstrate that the mechanism of action of the potent cytotoxic agent 5-nitro-2'-deoxyuridine (NO2-dUrd) involves thymidine (dThd) kinase catalyzed formation of 5-nitro-2'-deoxyuridylate (NO2dUMP) and subsequent potent inhibition of thymidylate (dTMP) synthetase by this compound. The evidence for this is as follows: (a) cells lacking dThd kinase are not inhibited by high concentrations of NO2dUrd; (b) the drug has no effect on dThd or uridine (Urd) incorporation into nucleic acids but prevents incorporation of deoxyuridine (dUrd); (c) growth inhibition is reversed by dThd but not by dUrd; (d) NO2dUrd causes changes in deoxynucleoside triphosphate pool sizes which are characteristic of specific inhibition of dTMP synthetase; (e) cells treated with [3H]NO2dUrd possess macromolecular bound [3H]NO2dUMP, which has properties characteristic of the NO2dUMP-dTMP synthetase complex. Treatment of L1210 leukemic mice at 400 mg/kg daily for 6 days gave only a 33% increase in life span, probably because of its rapid degradation to the inactive nitrouracil.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-nitro-2'-deoxyuridine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyuridine,
http://linkedlifedata.com/resource/pubmed/chemical/RNA
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1252-5
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:6183429-Adenosine Triphosphate,
pubmed-meshheading:6183429-Animals,
pubmed-meshheading:6183429-Antineoplastic Agents,
pubmed-meshheading:6183429-Cells, Cultured,
pubmed-meshheading:6183429-DNA,
pubmed-meshheading:6183429-Deoxyuridine,
pubmed-meshheading:6183429-Female,
pubmed-meshheading:6183429-Leukemia L1210,
pubmed-meshheading:6183429-Mice,
pubmed-meshheading:6183429-RNA,
pubmed-meshheading:6183429-Time Factors
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pubmed:year |
1982
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pubmed:articleTitle |
Mechanism of action of 5-nitro-2'-deoxyuridine.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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