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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1993-7-21
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pubmed:abstractText |
Trifluoperazine (TFP) is effective in modulating DNA damage/repair in doxorubicin (DOX) treated cells. In the present study we have characterised the resistance phenotype of parental sensitive L1210 mouse leukaemia cells (L1210/S) adapted to grow in the presence of 0.017 microns DOX+5 microM TFP (L1210/DT). Although with prolonged exposure, 0.017 microM DOX alone produced < 35% cell kill in L1210/S cells, similar cytotoxicity was achieved at 0.43 microM DOX in L1210/S cells selected in the presence of 0.017 microM DOX+5 microM TFP. L1210/DT cells were > 30-fold resistant to DOX following a 3 h drug exposure in a soft agar colony assay. In contrast, DOX sensitivity in cells adapted to grow in 5 microM TFP alone was comparable to L1210/S cells. Resistance to other inhibitors of topoisomerase II in L1210/DT cells was > 30-fold to etoposide and > 6-fold to amsacrine. The levels of the 170 kDa and 180 kDa isoforms of topoisomerase II in an immunoblot were comparable between the L1210/S and L1210/DT cells. Cross resistance to vincristine in the L1210/DT cells was accompanied by the overexpression of plasma membrane P-glycoprotein. Although a 1.5-2-fold decrease in accumulation of etoposide and DOX was observed in the L1210/DT cells, drug levels for equivalent DNA damage in the alkaline elution assay were > 5-fold higher in the L1210/DT versus L1210/S cells. No abrogation in the modulating effects of TFP on DOX, VP-16 or amsacrine induced cytotoxicity was apparent in the L1210/DT cells. Results suggest that: (a) TFP in combination with low concentrations DOX can induce the selection of cells with the multidrug resistant phenotype; and (b) characteristics of cells selected for resistance to DOX or DOX plus TFP are comparable.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-1670962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-1674871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-1676918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-1968761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-1972154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-1995027,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-2217530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-2222519,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-2570548,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-2576973,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-3342075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-3390370,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-3843705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-388439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-5432063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-6361451,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-6540180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099806-6861140
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Trifluoperazine
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1203-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8099806-Animals,
pubmed-meshheading:8099806-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:8099806-Calmodulin,
pubmed-meshheading:8099806-Carrier Proteins,
pubmed-meshheading:8099806-Cell Division,
pubmed-meshheading:8099806-DNA, Neoplasm,
pubmed-meshheading:8099806-DNA Damage,
pubmed-meshheading:8099806-DNA Topoisomerases, Type II,
pubmed-meshheading:8099806-Doxorubicin,
pubmed-meshheading:8099806-Drug Resistance,
pubmed-meshheading:8099806-Drug Screening Assays, Antitumor,
pubmed-meshheading:8099806-Etoposide,
pubmed-meshheading:8099806-Leukemia L1210,
pubmed-meshheading:8099806-Membrane Glycoproteins,
pubmed-meshheading:8099806-Mice,
pubmed-meshheading:8099806-P-Glycoprotein,
pubmed-meshheading:8099806-Phenotype,
pubmed-meshheading:8099806-Trifluoperazine,
pubmed-meshheading:8099806-Tumor Cells, Cultured
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pubmed:year |
1993
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pubmed:articleTitle |
Calmodulin inhibitor trifluoperazine in combination with doxorubicin induces the selection of tumour cells with the multidrug resistant phenotype.
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pubmed:affiliation |
Department of Cancer Biology, Cleveland Clinic Foundation, Ohio 44195.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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