Document Detail

Establishment of human KB cells resistant to 1-beta-D-arabinofuranosylcytosine, and mechanisms of cellular resistance in isolated clones.
MedLine Citation:
PMID:  6489676     Owner:  NLM     Status:  MEDLINE    
A subline of human KB cells that was resistant to 1-beta-D-arabinofuranosylcytosine (ara-C) was established by continuous exposure of the cells to increasing concentrations of ara-C. Thirteen resistant clones were isolated from the resistant subline (KB/ara-C). KB/ara-C showed 1,300-fold higher resistance than the parent KB cells to ara-C; the most resistant clones, clones 7 and 10, showed 1,330-fold higher resistance. In the absence of ara-C, the resistance of the parent KB/ara-C cells was stable for at least 14 weeks, whereas that of clone 7 was stable for 10 weeks, but was slightly less after 14 weeks. The ara-C kinase and ara-C deaminase activities of the 13 clones and the cellular uptake of ara-C by several clones were measured. In general the clones showed decreased deoxycytidine kinase activity and decreased cellular uptake of ara-C. Most clones had higher cytidine deaminase activity than KB cells, but some had activity similar to that of the KB cells. A clear inverse relationship was found between the ara-C sensitivity of the clones and their kinase activity, but not their deaminase activity or their ara-C uptake. These results clearly demonstrate that a major mechanism of ara-C resistance of these human KB cells was a decrease in the activity of the ara-C activating enzyme deoxycytidine kinase. The parent KB/ara-C cells showed no clear cross-resistance to various antitumor agents other than an ara-C derivative, including metabolic inhibitors, alkylating agents, DNA binders and mitotic spindle poisons.
T Tsuruo; K Naganuma; H Iida; S Sone; K Ishii; E Tsubura; S Tsukagoshi; Y Sakurai
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Gan     Volume:  75     ISSN:  0016-450X     ISO Abbreviation:  Gan     Publication Date:  1984 Aug 
Date Detail:
Created Date:  1984-11-28     Completed Date:  1984-11-28     Revised Date:  2014-10-03    
Medline Journal Info:
Nlm Unique ID:  0151745     Medline TA:  Gan     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  690-8     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / pharmacology
Clone Cells / drug effects
Cytarabine / metabolism,  pharmacology*
Cytidine Deaminase / analysis
Deoxycytidine Kinase / analysis
Drug Resistance
KB Cells / drug effects*
Reg. No./Substance:
0/Antineoplastic Agents; 04079A1RDZ/Cytarabine; EC Kinase; EC Deaminase

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