Long term cultured HL-60 cells are intrinsically resistant to Ara-C through high CDA activity.
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.
Department of Pediatrics, Tongji Hospital, Tongji University school of medicine, Shanghai 200065, China.
Jinqing
J
Tang
Xiaotian
X
Xie
Xiaoping
X
Zhang
Xiaohong
X
Qiao
Shayi
S
Jiang
Wei
W
Shi
Yuexia
Y
Shao
Xiaoxun
X
Zhou
D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism; D001086:Arabinofuranosyluracil / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate; D001086:Arabinofuranosyluracil; D003564:Cytidine Deaminase