Differential protection of normal and malignant human myeloid progenitors (CFU-GM) from ara-C toxicity using cycloheximide

C. A. Slapak, R. L. Fine, Carol M Richman

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Cycloheximide, a reversible protein sythesis 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 increased 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.

Original languageEnglish (US)
Pages (from-to)830-834
Number of pages5
JournalBlood
Volume66
Issue number4
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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