IN-VITRO SYNERGISTIC INHIBITION OF HUMAN BONE-MARROW HEMATOPOIETIC PROGENITOR GROWTH BY A 3'-AZIDO-3'-DEOXY-THYMIDINE, 2',3'-DIDEOXYCYTIDINE COMBINATION

In vitro growth of human normal bone marrow granulocyte-macrophage col ony forming units (CFU-GMs) and erythroid burst forming units (BFU-Es) was dose-dependently inhibited by 3'-azido-3'deoxythymidine (AZT) (fr om 0.1 mu M to 4 mu M) and 2',3'-dideoxycytidine (ddC) (from 0.01 mu M to 1.0 mu M) These ranges included minimum in vitro inhibitory concen trations to HIV-1 and concentrations corresponding to plasma level ach ievable in vivo. A synergistic inhibitory effect, statistically highly significant, was observed when combinations of the two drugs were add ed to cultures. This severe in vitro toxicity of ddC and the synergist ic toxicity of AZT-ddC combinations on hemopoietic progenitor cells sh ould be considered when the two drugs are administered in concurrent o r alternating regimens.