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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1993-3-10
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pubmed:abstractText |
Thymidine kills cells by depleting dCTP stores. The present experiments tested whether deoxycytidine, by replenishing dCTP pools, could prevent thymidine cytotoxicity and thymidine's enhancement of carboplatin killing in two human T-cell acute leukemia cell lines. MOLT3 and JM cells were exposed to combinations of thymidine, deoxycytidine, and carboplatin and then assessed for survival, the magnitude of thymidine-carboplatin chemosensitization, and changes in deoxyribonucleoside triphosphate pools. For both cell lines, deoxycytidine (up to 144.5 micrograms/ml x 24 h) completely restored dCTP pools but only partially protected against thymidine cytotoxicity (100-1000 micrograms/ml x 24 h) and thymidine-carboplatin sensitization (up to 60 micrograms carboplatin/ml during the last hour of thymidine). This contrasts with complete protection in prior studies using other cell types. Thymidine alone markedly increased dTTP and dGTP pools and decreased dCTP; dATP pools underwent a sharp decline which has not been observed before in any cell line. In subsequent studies 0.0336-137.3 micrograms deoxyadenosine/ml partially prevented cytotoxicity and carboplatin sensitization by 300 micrograms thymidine/ml. Together, deoxycytidine and deoxyadenosine completely prevented thymidine-carboplatin sensitization even though dATP and dCTP pools were not entirely returned to normal. These findings are discussed in regard to the unusual sensitivity of T-cell malignancies to thymidine toxicity, mechanisms of cytotoxicity and chemosensitization by thymidine, and the possibility of thymidine selectively sensitizing T-cell malignancies to killing by alkylating agents.
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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/Carboplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyadenosines,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytidine,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0145-2126
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
167-74
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8429693-Carboplatin,
pubmed-meshheading:8429693-Deoxyadenosines,
pubmed-meshheading:8429693-Deoxycytidine,
pubmed-meshheading:8429693-Deoxyribonucleotides,
pubmed-meshheading:8429693-Humans,
pubmed-meshheading:8429693-Leukemia, T-Cell,
pubmed-meshheading:8429693-Thymidine,
pubmed-meshheading:8429693-Tumor Cells, Cultured
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pubmed:year |
1993
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pubmed:articleTitle |
Deoxyribonucleoside triphosphate pools and thymidine chemosensitization in human T-cell leukemia.
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pubmed:affiliation |
Division of Hematology-Oncology, Denver Veterans Administration Medical Center, CO 80220.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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