Differential Effects of Deoxyadenosine and Deoxyguanosine on Dna

J. M. Wilson is a National Science Foundation Predoctoral Fellow. Dr. Mitchell is the recipient of National Institutes of Health Clinical Investigator Award 1 K08 AM 00442. Received for publication 17 January 1979 and in revised form 23 July 1979. reducing incorporation into the deoxyribonucleotide pool. In contrast, deoxyadenosine plus EHNA did not show this differential inhibition of [3H]uridine incorporation into DNA, and the alteration in [3H]cytidine incorporation into nucleotide pools was less impressive. These data show an association between accumulation of dATP or dGTP and a primary inhibition of DNA synthesis, and they provide support for ribonucleotide reductase inhibition as the mechanism responsible for deoxyguanosine toxicity. Deoxyadenosine toxicity, however, appears to result from another, or perhaps a combination of, molecular event(s).