Studies on the cellular pharmacology of antiretroviral dideoxynucleosides have continued. We have observed that the anabolism of dideoxycytidine to its active form, ddCTP, is highly variable in both normal and neoplastic humans cells, being sluggish in thoracic duct lymphocytes, energetic in monocytes and vigorous in ATH-8 T-lymphocytes. We also established that dideoxyadenosine, in contrast to dideoxycytidine, is catabolized extensively, both before but especially after its passage into cells. Since adenylate deaminase accepts ddAMP as a substrate, and since dCF is not an effective inhibitor of this reaction, it is proposed that at least some of the catabolism of ddA is inaugurated at the level of its 5'-monophosphate, especially in the presence of dCF. As a consequence of the preponderant catabolism of ddA, only low levels of ddATP 950-100 nM) are detectable in cells treated with this nucleoside; these low levels must, nevertheless, be adequate to inhibit the reverse transcriptase of the HIV and block its replication.
