S-Adenosylhomocysteine Hydrolase Inhibition in Deoxyadenosine-Treated Human T-Lymphoblasts and Resting Peripheral Blood Lymphocytes

Richard F. Kefford*, Megan A. Helmer, Richard M. Fox

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The pattern of inhibition and recovery of intracellular S-adenosylhomocysteine hydrolase (AdoHcyase) activity induced by cytotoxic concentrations of 2’-deoxyadenosine (dAdo) in the presence of the adenosine deaminase inhibitor erythro-9-[3-(2-hydroxynonyl)]adenine was studied in cultured human T-lymphoblasts (CCRF-CEM and -HSB), Epstein-Barr virus-transformed B-lymphoblasts (JP and RDG), and resting peripheral blood lymphocytes. In the presence of 5 derythro-9-[3-(2-hydroxynonyl)]adenine the AdoHcyase activity was inhibited 50% after 1 hr of incubation by 3, 10, and 30 dAdo for B-lymphoblasts, T-lymphoblasts, and peripheral blood lymphocytes, respectively, while cytotoxicity (to 50% of controls) was effected by 600,3, and 1 µM dAdo, respectively. Cytostatic concentrations of dAdo, which induce G1-phase arrest in T-lymphoblasts, inhibited AdoHcyase to 30% of control at 4 hr, after which recovery to normal levels occurred over 24 hr. Coincubation with 50 µM 2#-deoxycytidine, which protects these cells from both G1-phase arrest and growth inhibition by dAdo, had no effect on the pattern of inhibition of AdoHcyase activity. Epstein-Barr virus-transformed B-lymphoblasts exposed to the same concentrations of dAdo were not growth inhibited but displayed patterns of AdoHcyase inhibition closely similar to those seen in T-lymphoblasts. Coincubation with 20 µM 2’-deoxycytidine, despite its protective effect againt dAdo cytotoxicity, had no effect on the pattern of AdoHcyase inhibition in resting peripheral blood lymphocytes induced by 10 µM dAdo and 5 erythro-9-[3-(2-hydroxynonyl)]adenine over a 72-hr period. The lack of correlation between cytotoxicity and AdoHcyase inhibition in human lymphoid cells suggest that other mechanisms may account for the toxic effects of dAdo in these cells.

Original languageEnglish
Pages (from-to)3822-3827
Number of pages6
JournalCancer Research
Volume42
Issue number9
Publication statusPublished - 1 Sep 1982
Externally publishedYes

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