The influence of 2-chloro-2'-deoxyadenosine on metabolism of deoxyadenosine in human primary CNS lymphoma

Fabianowskamajewska, K, Tybor, K, Duley, J and Simmonds, A (1995) The influence of 2-chloro-2'-deoxyadenosine on metabolism of deoxyadenosine in human primary CNS lymphoma. Biochemical Pharmacology, 50 9: 1379-1383. doi:10.1016/0006-2952(95)02018-7


Author Fabianowskamajewska, K
Tybor, K
Duley, J
Simmonds, A
Title The influence of 2-chloro-2'-deoxyadenosine on metabolism of deoxyadenosine in human primary CNS lymphoma
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 1995-01-01
Year available 1995
Sub-type Article (original research)
DOI 10.1016/0006-2952(95)02018-7
Open Access Status Not yet assessed
Volume 50
Issue 9
Start page 1379
End page 1383
Total pages 5
Place of publication OXFORD
Publisher PERGAMON-ELSEVIER SCIENCE LTD
Language eng
Subject 1303 Specialist Studies in Education
3004 Pharmacology
Abstract The effects of 2-chloro-2'-deoxyadenosine (2CdA) on the activity of enzymes important for the metabolism of deoxyadenosine were studied in lysates prepared from human primary central nervous system (CNS) lymphomas and normal human lymphocytes. Strong inhibition (approximately 100%) of the phosphorylation of deoxyadenosine to its deoxynucleotide phosphate derivatives was produced in both systems in the presence of 2CdA, which was phosphorylated concomitantly to 2-chloro-2'-deoxyAMP. Interestingly, 2CdA was also found to be an inhibitor of the deamination of both deoxyadenosine (over 50%) and AMP (70%). These findings add to our understanding of the mechanisms of toxicity of this drug, especially considering that 2CdA is resistant to deamination by adenosine deaminase. These results challenge the existing theories of 2CdA toxicity, which have been limited to the formation of phosphate derivatives of 2CdA. The present in vitro studies have demonstrated that 2CdA also inhibits both phosphorylation and deamination of deoxyadenosine (dAdo), suggesting that its mechanism of toxicity includes a block in dAdo metabolic pathways. This has important implications for the perturbation of cell methylation, a functionality associated with, for example, apoptosis.
Keyword 2-chloro-2'-deoxyadenosine
Cladribine
CNS lymphoma cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: ResearcherID Downloads - Archived
 
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