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.
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Authors | Jinqing Tang, Xiaotian Xie, Xiaoping Zhang, Xiaohong Qiao, Shayi Jiang, Wei Shi, Yuexia Shao, Xiaoxun Zhou |
Journal | Frontiers in bioscience (Landmark edition)
(Front Biosci (Landmark Ed))
Vol. 17
Issue 2
Pg. 569-74
(01 01 2012)
ISSN: 2768-6698 [Electronic] Singapore |
PMID | 22201761
(Publication Type: Journal Article)
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Chemical References |
- RNA, Messenger
- RNA, Neoplasm
- Cytarabine
- Arabinofuranosylcytosine Triphosphate
- Arabinofuranosyluracil
- Cytidine Deaminase
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Topics |
- Arabinofuranosylcytosine Triphosphate
(metabolism)
- Arabinofuranosyluracil
(metabolism)
- Cytarabine
(pharmacology)
- Cytidine Deaminase
(genetics, metabolism)
- Drug Resistance, Neoplasm
(physiology)
- HL-60 Cells
- Humans
- RNA, Messenger
(genetics, metabolism)
- RNA, Neoplasm
(genetics, metabolism)
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