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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
20
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pubmed:dateCreated |
1990-11-21
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pubmed:abstractText |
In this study we describe the establishment of a leukemic cell line (BNML-CL/ara-C), originating from the 1-beta-D-arabinofuranosylcytosine (ara-C)-resistant brown Norway rat myelocytic leukemia model (BNML/ara-C), that retains the in vivo generated ara-C resistance. Its biological and biochemical characteristics have been compared with a cell line, derived from the ara-C-sensitive BNML model (BNML-CL/O). Resistance to ara-C was attributed to a decrease in phosphorylation of ara-C. Deoxycytidine (dCyd) kinase activity in crude cell extracts with dCyd as substrate showed similar enzyme activities in both cell lines, whereas with ara-C as substrate no dCyd kinase activity was detectable in the ara-C-resistant cell line. Two isoenzymes of dCyd kinase with different substrate specificities have been described (Cheng, Y.C., Domin, B., and Lee, L.S. Biochim. Biophys. Acta, 481: 481-492, 1977), cytoplasmic (dCyd kinase I, substrates: dCyd and ara-C) and mitochondrial (dCyd kinase II, substrates: dCyd and thymidine). In the ara-C-sensitive BNML model, thymidine induced a reduction of dCyd kinase activity when dCyd was used as substrate. However, thymidine did not affect kinase activity with ara-C was used as substrate. In the BNML-CL/ara-C, thymidine even induces a dCyd kinase inhibition of 85% with dCyd as substrate. It is likely that the ara-C-specific dCyd kinase deficiency in BNML-CL/ara-C cells was due to a selective loss of dCyd kinase I, whereas dCyd kinase II activity remained intact.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6515-9
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:2208110-Animals,
pubmed-meshheading:2208110-Cell Survival,
pubmed-meshheading:2208110-Chromosome Aberrations,
pubmed-meshheading:2208110-Cytarabine,
pubmed-meshheading:2208110-Deoxycytidine Kinase,
pubmed-meshheading:2208110-Deoxyribonucleotides,
pubmed-meshheading:2208110-Drug Resistance,
pubmed-meshheading:2208110-Isoenzymes,
pubmed-meshheading:2208110-Leukemia, Myeloid,
pubmed-meshheading:2208110-Rats,
pubmed-meshheading:2208110-Rats, Inbred BN,
pubmed-meshheading:2208110-Substrate Specificity,
pubmed-meshheading:2208110-Tumor Cells, Cultured
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pubmed:year |
1990
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pubmed:articleTitle |
Substrate-specific deoxycytidine kinase deficiency in 1-beta-D-arabinofuranosylcytosine-resistant leukemic cells.
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pubmed:affiliation |
Department of Hematology, Leiden University Medical Center, The Netherlands.
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pubmed:publicationType |
Journal Article
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