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Specific toxicity of 2-chlorodeoxyadenosine toward resting and
proliferating human lymphocytes
DA Carson, DB Wasson, R Taetle and A Yu
2-Chlorodeoxyadenosine (CdA), an adenosine-deaminase-resistant purine
deoxynucleoside, is markedly toxic toward human T-lymphoblastoid cell lines
in vitro and is an effective agent against L1210 leukemia in vivo. The
present studies have examined the toxicity, and in some cases, metabolism,
of CdA in (1) multiple established human cell lines of varying phenotype,
(2) leukemia and lymphoma cells taken directly from patients, (3) normal
bone marrow cells, and (4) normal peripheral blood lymphocytes. Nanomolar
concentrations of CdA blocked the proliferation of lymphoblastoid cell
lines with a high ratio of deoxycytidine kinase to deoxynucleotidase. The
drug had virtually no effect on the growth of cell lines derived from solid
tissues. The CdA inhibited the spontaneous uptake of tritiated thymidine by
many T and non-T, non-B acute lymphoblastic leukemia cell specimens at
concentrations less than or equal to 5 nM. The same concentrations did not
impair either thymidine uptake or granulocyte-monocyte colony formation by
normal bone marrow cells. In common with deoxyadenosine, but unlike several
other agents affecting purine and purine metabolism, CdA was lethal to
resting normal T lymphocytes and to slowly dividing malignant T cells. In
both resting and proliferating lymphocytes, the CdA was phosphorylated by
deoxycytidine kinase and entered a rapidly turning over nucleotide pool.
Dividing lymphocytes also incorporated abundant CdA into DNA. The selective
toxicity of CdA toward both dividing and resting lymphocytes may render the
drug useful as an immunosuppressive or antileukemic agent.
Volume 62,
Issue 4,
pp. 737-743,
10/01/1983
Copyright © 1983 by The American Society of Hematology
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