Flow Cytometric Analysis of Adenosine Analogue Lymphocytotoxicity

Richard F. Kefford, Ian W. Taylor, Richard M. Fox*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The induction of G1-phase arrest in T-iymphoblasts by cytostatic concentrations of 2’-deoxyadenosine (R. M. Fox, R. F. Kefford, E. H. Tripp, and I. W. Taylor, Cancer Res., 41: 5141–5150,1981) prompted a flow cytometric analysis of the cell cycle effects of three other adenosine analogues with known effects on polyadenylated RNA metabolism in an attempt to further explore the nature of 2’-deoxyadenosine 5’-triphosphate-mediated lymphotoxicity. Cytostatic concentrations of 9- ß-D-arabi-nofuranosyladenine induced an S-phase block, while 3’-deoxy-adenosine (cordycepin) and tubercidin (7-deazaadenosine) induced a cycle-nonspecific block. Furthermore, total cellular RNA content was unaltered by 2’-deoxyadenosine or 9- ß-D-arabino-furanosyladenine, but 3’-deoxyadenosine and tubercidin caused a marked reduction in total cellular RNA at minimally cytostatic concentrations. At concentrations of 0.3 to 20 μm, all of these nucleosides were toxic to nondividing peripheral blood lymphocytes, suggesting that in these cells their mechanism of action does not involve reactions associated with DNA replication. Inhibition of polyadenylated RNA metabolism by triphosphate derivatlves of adenosine analogues may account for lymphocytotoxicity in nondividing cells, but the demonstrated diverse effects of these nucleosides on nucleic acid metabolism in dividing cells preclude elucidation of the mechanism of the unique induction of G1-phase arrest by 2’-deoxyadenosine.

Original languageEnglish
Pages (from-to)5112-5119
Number of pages8
JournalCancer Research
Volume43
Issue number11
Publication statusPublished - 1 Nov 1983
Externally publishedYes

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