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RNAi Depletion of Deoxycytidine and Deoxyguanosine Kinase in Human Leukemic CEM Cells
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska University Hospital, Stockholm.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology. Linköping University, Faculty of Health Sciences.
2008 (English)In: Nucleosides, Nucleotides & Nucleic Acids, ISSN 1525-7770, E-ISSN 1532-2335, Vol. 27, no 6-7, 712-719 p.Article in journal (Refereed) Published
Abstract [en]

Resistance toward nucleoside analogues is often due to decreased activities of the activating enzymes deoxycytidine kinase (dCK) and/or deoxyguanosine kinase (dGK). With small interfering RNA (siRNA), dCK and dGK were downregulated by approximately 70% in CEM cells and tested against six nucleoside analogues using the methyl thiazol tetrazolium assay. SiRNA-transfected cells reduced in dCK activity were 3- to 6-fold less sensitive to CdA, AraC, and CAFdA. The sensitivity to AraG and FaraA was unchanged, while the sensitivity toward gemcitabine was significantly increased. dGK depletion in cells resulted in lower sensitivity to FaraA, dFdC, CAFdA, and AraG, but slightly higher sensitivity to CdA and AraC.

Place, publisher, year, edition, pages
2008. Vol. 27, no 6-7, 712-719 p.
Keyword [en]
deoxycytidine kinase, deoxyguanosine kinase, nucleoside analogue, resistance, RNA interference
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-45875DOI: 10.1080/15257770802145231OAI: oai:DiVA.org:liu-45875DiVA: diva2:266771
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved

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Fyrberg, AnnaAlbertioni, FreidounLotfi, Kourosh

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Fyrberg, AnnaAlbertioni, FreidounLotfi, Kourosh
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Clinical PharmacologyFaculty of Health SciencesDepartment of Haematology
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