Open Access
Long term cultured HL-60 cells are intrinsically resistant to Ara-C through high CDA activity
Jinqing Tang1,Xiaotian Xie1,*,Xiaoping Zhang2,Xiaohong Qiao1,Shayi Jiang1,Wei Shi1,Yuexia Shao1,Xiaoxun Zhou1
Department of Pediatrics, Tongji Hospital, Tongji University school of medicine, Shanghai 200065, China
Department of Nuclear Medicine, Shanghai tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
DOI: 10.2741/3944 Volume 17 Issue 2, pp.569-574
Published: 01 January 2012
(This article belongs to the Special Issue Pathogenesis and diagnostic modalities in cancer)
*Corresponding Author(s):  
Xiaotian Xie

Cytarabine (araC) is a highly active antimetabolite against hematological malignancy while the agent shows limited activity for some patients despite maintenance or continued therapy with ara-C-containing regiments. In this study, we focused to elucidate the mechanism of intrinsic resistance to araC. The concentration of intracellular ara-CTP and incorporated ara-CTP were monitored in human leukemia cell line-HL-60 for different passages in parental with its variant HL-60R. The expression of mRNA for deoxycytidine kinase (dCK), cytidine deaminas (CDA), human equilibrative nucleoside transporter 1 (hENT1), and cytosolic 50-nucleotidase II (cN-II) were examined by Real-time PCR in HL-60 and HL-60R for different passages. And activities of two metabolizing enzymes for araC, dCK and CDA were further examined. The results showed that the concentration of intracellular ara-CTP was significantly reduced and the ara-U increased in HL-60 cells for 50 passages compared with the 5 passages, and associated with higher CDA activity. All the factors in HL-60R cells did not change by the incubation of ara-C. In conclusion, the long term cultured cells are intrinsically resistant to ara-C through high CDA activity, but not low DCK activity.

Key words

Cytarabine; HL-60; CDA Activity; Leukemic Cells

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Jinqing Tang, Xiaotian Xie, Xiaoping Zhang, Xiaohong Qiao, Shayi Jiang, Wei Shi, Yuexia Shao, Xiaoxun Zhou. Long term cultured HL-60 cells are intrinsically resistant to Ara-C through high CDA activity. Frontiers in Bioscience-Landmark. 2012. 17(2); 569-574.