In vitro synergistic inhibition of human bone marrow hemopoietic progenitor growth by a 3'-azido-3'-deoxy-thymidine, 2',3'-dideoxycytidine combination.
In vitro growth of human normal bone marrow granulocyte-macrophage colony forming units (CFU-GMs) and erythroid burst forming units (BFU-Es) was dose-dependently inhibited by 3'-azido-3'deoxythymidine (AZT) (from 0.1 microM to 4 microM) and 2',3'-dideoxycytidine (ddC) (from 0.01 microM to 1.0 microM). These ranges included minimum in vitro inhibitory concentrations to HIV-1 and concentrations corresponding to plasma level achievable in vivo. A synergistic inhibitory effect, statistically highly significant, was observed when combinations of the two drugs were added to cultures. This severe in vitro toxicity of ddC and the synergistic toxicity of AZT-ddC combinations on hemopoietic progenitor cells should be considered when the two drugs are administered in concurrent or alternating regimens.
Lerza
R
R
Department of Internal Medicine, University of Genoa, Italy.
Castello
G
G
Mela
G S
GS
Arboscello
E
E
Cerruti
A
A
Bogliolo
G
G
Mencoboni
M
M
Ballarino
P
P
Pannacciulli
I
I
D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D004920:Erythropoiesis / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D016047:Zalcitabine / Q000008:administration & dosage*; D015215:Zidovudine / Q000008:administration & dosage*
D015215:Zidovudine; D016047:Zalcitabine