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Effects of 2-chloro-2'-deoxyadenosine on the cell cycle in the human leukemia EHEB cell line.

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Cardoen, S. Van Den Neste, Eric [UCL] Smal, Caroline [UCL] Rosier, Jean-Claude [UCL] Ferrant, Augustin [UCL] Van den Berghe, Georges [UCL] Bontemps, Françoise [UCL]

To explain why 2-chloro-2'-deoxyadenosine (CdA) is unable to block DNA synthesis and cell cycle progression, and paradoxically enhances progression from G1 into S phase in the CdA-resistant leukemia EHEB cell line, we studied its metabolism and effects on proteins regulating the transition from G1 to S phase. A low deoxycytidine kinase activity and CdATP accumulation, and a lack of p21 induction despite p53 phosphorylation and accumulation may account for the inability of CdA to block the cell cycle. An alternative pathway involving pRb phosphorylation seems implicated in the CdA-induced increase in G1 to S phase progression.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2004
Journal information "Nucleosides, Nucleotides and Nucleic Acids : an international journal for rapid communication" - Vol. 23, no. 8-9, p. 1425-1429 (2004)
Peer reviewed yes
Publisher Taylor & Francis Inc. (Philadelphia)
issn 1525-7770
e-issn 1532-2335
Publication status Publié
Affiliations UCL - MD/BICL - Département de biochimie et de biologie cellulaire
UCL - MD/MINT - Département de médecine interne
UCL - (SLuc) Service d'hématologie
MESH Subject Antimetabolites, Antineoplastic - pharmacology ; Antineoplastic Agents - pharmacology ; Blotting, Western ; Bromodeoxyuridine - pharmacology ; Cell Cycle ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Cladribine - pharmacology ; Cyclin-Dependent Kinase Inhibitor p21 ; DNA - biosynthesis - metabolism ; Deoxycytidine Kinase - metabolism ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - metabolism ; Flow Cytometry ; G1 Phase ; Humans ; Inhibitory Concentration 50 ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy - metabolism ; Models, Biological ; Phosphorylation ; S Phase ; Time Factors
Keywords 2-Chloro-2'-deoxyadenosine ; CdA resistance ; G1/S transition ; Cell cycle ; pRb ; B-CLL
Links
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Bibliographic reference Cardoen, S. ; Van Den Neste, Eric ; Smal, Caroline ; Rosier, Jean-Claude ; Ferrant, Augustin ; et. al. Effects of 2-chloro-2'-deoxyadenosine on the cell cycle in the human leukemia EHEB cell line.. In: Nucleosides, Nucleotides and Nucleic Acids : an international journal for rapid communication, Vol. 23, no. 8-9, p. 1425-1429 (2004)
Permanent URL http://hdl.handle.net/2078.1/10037