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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1990-10-22
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pubmed:abstractText |
Two human ovarian cancer cell lines were established from a patient before (PEO1) and after (PEO4) the onset of resistance to 5-fluorouracil (5-FU)/cisplatin-based chemotherapy. Using growth inhibition assays, we determined that the PEO4 line was almost 5-fold more resistant to 5-FU than the PEO1 line. The addition of either 1 or 20 microM leucovorin did not enhance the growth-inhibitory effects of 5-FU against the resistant PEO4 line. In characterizing the potential mechanisms of 5-FU resistance, we found no differences in thymidylate synthase activity between the two lines using both the 5-fluoro-2'-deoxyuridine-5'-monophosphate-binding and catalytic assays. A 4-hr exposure to 1 microM 5-FU resulted in greater ternary complex formation in the resistant line, and we observed no differences between the two lines in 5-FU incorporation into RNA. However, a 4-hr exposure to 1 microM [3H]5-FU resulted in a 3-fold decrease in 5-FU accumulation in the DNA of the resistant PEO4 line. Cesium sulfate gradient centrifugation was used to more accurately separate and analyze for DNA-incorporated 5-FU metabolites and confirmed that the absolute level of 5-FU in the DNA of the PEO4 cells was markedly decreased (6.5-fold) compared with that of the sensitive PEO1 cell line. Moreover, time course studies demonstrated that the accumulated 5-FU in the DNA of the PEO4 cells was more rapidly removed compared with that in the PEO1 cells. Our findings suggest that decreased 5-FU levels in DNA, in part due to an enhanced removal from DNA, represent a mechanism by which the human ovarian cancer PEO4 line expresses decreased sensitivity to 5-FU.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2'-deoxyuridylic acid,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyuracil Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidylate Synthase
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
410-7
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:2402230-DNA, Neoplasm,
pubmed-meshheading:2402230-DNA Repair,
pubmed-meshheading:2402230-Deoxyuracil Nucleotides,
pubmed-meshheading:2402230-Drug Resistance,
pubmed-meshheading:2402230-Female,
pubmed-meshheading:2402230-Fluorouracil,
pubmed-meshheading:2402230-Humans,
pubmed-meshheading:2402230-Ovarian Neoplasms,
pubmed-meshheading:2402230-RNA, Neoplasm,
pubmed-meshheading:2402230-Thymidylate Synthase,
pubmed-meshheading:2402230-Tumor Cells, Cultured
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pubmed:year |
1990
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pubmed:articleTitle |
Resistance of a human ovarian cancer line to 5-fluorouracil associated with decreased levels of 5-fluorouracil in DNA.
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pubmed:affiliation |
Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892.
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pubmed:publicationType |
Journal Article
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