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Cellosaurus publication CLPUB00209

Publication number CLPUB00209
Authors Toshio Kakihara;
Title The characterization of highly resistant human leukemic cell lines to 1-beta-D-arabinofuranosylcytosine.
Citation Acta Med. Biol. 39:119-127(1991)
Web pages https://hdl.handle.net/10191/33445
Abstract Two human myelomonocytic leukemia cell lines highly resistant to 1-beta-D- arabinofuranosylcytosine (ara-C) were established. One line, designated KY-Ra, has been proliferating with 1x10^-4 M ara-C for over one year. The other one, KY-Rb, has proliferated with 1x10-5 M N(4)-behenoyl-1-beta-D- arabinofuranosylcytosine (BH-AC) after it reached a proliferative capacity with 1x10^-6 M ara-C. These two ara-C-resistant cell lines have shown approximately 5,900 fold and 18,000 fold resistance to ara-C over the parental KY-821 cell line. The deoxycytidine kinase activity of each cell line was 0.39 (dCMP/min/mug protein) for KY-Ra, 0.26 for KY-Rb, 1.23 for KY-821. Deoxycytidine deaminase activities were almost identical. In drug accumulations, ara-C resistant cell lines showed a reduced uptake of ara-C during a 4 h exposure to 1 nM ara-C. After loading almost the same intracellular contents of drugs, ara-CTP accumulation decreased in two ara-C resistant cell lines, and the efflux rate was increased in KY-Ra. These results indicate that the decreased deoxycytidine kinase activity, which resulted in a decreased ara-CTP accumulation, is one of major mechanisms of the resistance, and suggest the possibility that an increase of the outward flux of ara-C is one mechanism of resistance. These cell lines may be useful for studying the refractoriness encountered in ara-C administration.
Cell lines CVCL_W294; KY-Ra
CVCL_5A05; KY-Rb