The combination of 2′-deoxyadenosine and deoxycoformycin is known to be markedly toxic to T-lymphocyte cell lines relative to B-cell lines, and this difference appears to be related to the capacity of the cells to accumulate deoxyadenosine triphosphate (dATP). In the presence of dipyridamole and 2′-deoxyadenosine and when adenosine deaminase was inhibited with deoxycoformycin, the L1210 leukemia cell which is a non-T-, non-B-cell type accumulated dATP like a T-cell type. The intracellular L1210 concentration of dATP using the triple combination (1.1 µm deoxycoformycin-40 µm deoxyadenosine-10 µm dipyridamole) reached 400 µm at which concentration ribonucleotide reductase specific activity was reduced by 80%. While this degree of enzyme may be significant, complete inhibition might have been expected, since 400 µm dATP is approximately 40 times the concentration to give 50% inhibition in some purified systems.
This research was supported by Grant CA-31634 from the National Cancer Institute and by Grant E-321 from the Robert A. Welch Foundation.