Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo

D. A. Carson, D. B. Wasson, J. Kaye, B. Ullman, D. W. Martin, R. K. Robins, J. A. Montgomery

Research output: Contribution to journalArticle

206 Scopus citations


An inherited deficiency of adenosine deaminase (adenosine aminohydrolase, EC produces selective lymphopenia and immunodeficiency disease in humans. Previous experiments have suggested that lymphospecific toxicity in this condition might result from the selective accumulation of toxic deoxyadenosine nucleotides by lymphocytes with high deoxycytidine kinase levels and low deoxynucleotide dephosphorylating activity. The present experiments were designed to determine if deoxyadenosine analogs which are not substrates for adenosine deaminase might similarly be toxic toward lymphocytes and lymphoid tumors. Two such compounds, 2-chlorodeoxyadenosine and 2-fluorodeoxyadenosine, at concentrations of 3 nM and 0.15 μM, respectively, inhibited by 50% the growth of human CCRF-CEM malignant lymphoblasts in vitro. Each was phosphorylated in intact cells by deoxycytidine kinase, accumulated as the nucleoside triphosphate, and inhibited DNA synthesis more than RNA synthesis. Both deoxynucleosides had significant chemotherapeutic activity against lymphoid leukemia L1210 in mice.

Original languageEnglish (US)
Pages (from-to)6865-6869
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number11 I
StatePublished - Dec 1 1980


ASJC Scopus subject areas

  • General

Cite this