Specific toxicity of 2-chlorodeoxyadenosine toward resting and proliferating human lymphocytes

To determine the potential lymphocyte-specific action of CdA, deoxyribonucleoside we have studied the effects of the on multiple established leukemia cell specimens at concentrations

DA Carson; DB Wasson; R Taetle; A Yu

2019

Scholarcy highlights

  • 2-Chlorodeoxyadenosine. an adenosine-deaminaseresistant purine deoxynucleoside, is markedly toxic toward human T-lymphoblastoid cell lines in vitro and is an effective agent against Li 21 0 leukemia in vivo
  • To determine the potential lymphocyte-specific action of CdA, deoxyribonucleoside we have studied the effects of the on multiple established leukemia cell specimens at concentrations
  • In both resting and proliferating lymphocytes, the CdA was phosphorylated by deoxycytidine kinase and entered a rapidly turning over nucleotide pool
  • The toxicity toward resting human peripheral blood lymphocytes of CdA and other drugs affecting purine and pyrimidine metabolism was determined as previously described for deoxyadenosine.’#{176} Briefly, peripheral blood mononuclear cells from normal subjects, suspended at a density of l06/ml in RPMI 1640 medium supplemented with 2 mM L-glutamine, 20% autologous plasma, and twofold increasing concentrations of the respective agents, were dispersed in microtiter trays in 0.2-mi aliquots
  • Of CdA inhibiting by 50% the proliferation of 10 different human cell lines growing in suspension culture
  • Neither intact lymphocytes nor cell extracts detectably catabolized CdA. These results suggest that CdA was phosphorylated by deoxycytidine kinase, converted to the 5’-triphosphate derivative, and incorporated into
  • These drugs are selectively toxic toward cells with high deoxycytidine kinase levels and low deoxynucleotidase activity, independent of growth rate

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