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Deoxyadenosine Metabolism and Toxicity in Cultured L5178Y Cells¹

University of Alberta Cancer Research Unit (McEachern Laboratory) and Department of Biochemistry, Edmonton, Alberta, Canada T6G 2H7

The growth of cultured L5178Y cells is inhibited by relatively low concentrations of deoxyadenosine in the presence of deoxycoformycin, an inhibitor of adenosine deaminase. Cell viability is reduced, presumably as a consequence of the induced state of unbalanced growth which is characterized by inhibition in DNA synthesis, accumulation of cells in G₁ or early S phase, a continuation in RNA synthesis, and increasing cell volume. The intracellular concentrations of purine and pyrimidine ribonucleoside phosphates remain essentially unchanged. The significant changes in the intracellular deoxynucleoside triphosphate pools are an increase in deoxyadenosine triphosphate and a decrease in deoxycytidine triphosphate.

¹ This work was supported by the National Cancer Institute and Medical Research Council of Canada.

² To whom requests for reprints should be addressed.

Received 12/17/76. Accepted 6/ 3/77.