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CA Slapak, RL Fine and CM Richman
Cycloheximide, a reversible protein synthesis inhibitor, is thought to
block DNA replication in normal cells by preventing synthesis of a labile
protein. In animal systems, cycloheximide protects normal cells from
cytotoxic S-phase specific agents, such as cytosine arabinoside (Ara-C).
Malignant cells appear not to be susceptible to cycloheximide- induced
cycle arrest and, subsequently, may not be protected from Ara-C
cytotoxicity. The effect of cycloheximide on granulocyte/macrophage
progenitors (CFU-GM) after in vitro Ara-C exposure was examined using
normal human bone marrow, malignant progenitors from patients with chronic
myelogenous leukemia (CML), and clonogenic cells from the human acute
nonlymphocytic leukemia cell lines HL-60 and KG-1. Mononuclear or
clonogenic cells were incubated for one hour with cycloheximide, followed
by the addition, for three or 17 hours, of Ara-C before being plated in a
methylcellulose culture system. CFU-GM survival was significantly increase
if normal cells were treated with cycloheximide before Ara-C exposure.
Similar cycloheximide pretreatment of CML progenitors and clonogenic HL-60
and KG-1 cells failed to protect CFU- GM from Ara-C-induced cytotoxicity.
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| Copyright © 1985 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||