G1-Phase Arrest of Cultured Human Leukemic T-Cells Induced by Deoxyadenosine

Cultured human T-cell leukemic lymphocytes have enhanced sensitivity to growth inhibition by deoxyadenosine. We have used flow cytometry to investigate the mechanism of deoxy-adenosine toxicity in cultured T-leukemic cells. Comparative studies on deoxyadenosine-resistant Epstein-Barr virus-trans-formed B-lymphocyte cell lines were also performed. After exposure of T-cells to low concentrations of deoxyadenosine (3 μm), in the presence of an adenosine deaminase inhibitor (erythro-9-{3-(2-hydroxynonyl)]adenosine), accumulation of cells of cells with a G1 DNA content was demonstrated. In contrast, B-cell lines showed a similar degree of growth inhibition after exposure to 200 to 400 μm deoxyadenosine but were blocked in S phase. The T-cell G1 block was associated with a rise in the deoxyadenosine triphosphate pool, and both these phenomena were prevented by the addition of deoxy-cytidine. The biochemical mechanism of this Gi block induced by deoxyadenosine in T-cells is not understood. Downloaded from cancerres.aacrjournals.org on February 9, 2016.