IMR Press / FBL / Volume 17 / Issue 2 / DOI: 10.2741/3944

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Long term cultured HL-60 cells are intrinsically resistant to Ara-C through high CDA activity
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1 Department of Pediatrics, Tongji Hospital, Tongji University school of medicine, Shanghai 200065, China
2 Department of Nuclear Medicine, Shanghai tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Academic Editor:Wei Qin
Front. Biosci. (Landmark Ed) 2012, 17(2), 569–574; https://doi.org/10.2741/3944
Published: 1 January 2012
(This article belongs to the Special Issue Pathogenesis and diagnostic modalities in cancer)
Abstract

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.

Keywords
Cytarabine
HL-60
CDA Activity
Leukemic Cells
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