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In vitro toxicity of 3′‐azido‐3′‐deoxythymidine, carbovir and 2′, 3′‐didehydro‐2′, 3′‐dideoxythymidine to human and murine haematopoietic progenitor cells
Author(s) -
Du DeLin,
Volpe Donna A.,
Grieshaber Charles K.,
Murphy Martin J.
Publication year - 1992
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1992.tb04555.x
Subject(s) - haematopoiesis , progenitor cell , in vitro , biology , in vivo , pharmacology , toxicity , virology , stem cell , immunology , microbiology and biotechnology , medicine , biochemistry , genetics
Summary The myelotoxicities of three antiretroviral agents, 3′‐azido‐3′‐deoxythymidine (AZT), carbovir (CBV) and 2′,3′‐didehydro‐2′,3′‐dideoxythymidine (d4T), were evaluated in vitro with normal human and murine haematopoietic progenitor cells. These studies demonstrated that continuous AZT exposure was more inhibitory to human and murine colony formation than 1 h exposure, with murine and human progenitors similarly inhibited by continuous AZT exposure. These in vitro results on AZT's myelotoxicity correlate with both human and murine in vivo studies. CBV was only moderately toxic to human and murine cells following either 1 h or continuous exposure, with human and murine progenitors similarly suppressed by continuous CBV exposure. 1 h d4T exposure was less toxic to both human and murine marrow cells than continuous exposure and both species were equivalently inhibited when continuously exposed to d4T. In general, CBV was the least toxic agent to human and murine haematopoietic cells and AZT the most toxic. The study establishes CBV and d4T as less myelotoxic agents to human and murine haematopoietic progenitor cells in vitro than AZT which therefore could be considered as alternatives to AZT for the treatment of HIV infection.