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 language | English (US) |
|---|---|
| Pages (from-to) | 830-834 |
| Number of pages | 5 |
| Journal | Blood |
| Volume | 66 |
| Issue number | 4 |
| State | Published - 1985 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Hematology
Cite this
Differential protection of normal and malignant human myeloid progenitors (CFU-GM) from ara-C toxicity using cycloheximide. / Slapak, C. A.; Fine, R. L.; Richman, Carol M.
In: Blood, Vol. 66, No. 4, 1985, p. 830-834.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential protection of normal and malignant human myeloid progenitors (CFU-GM) from ara-C toxicity using cycloheximide
AU - Slapak, C. A.
AU - Fine, R. L.
AU - Richman, Carol M
PY - 1985
Y1 - 1985
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0021966834&partnerID=8YFLogxK
M3 - Article
C2 - 3862435
AN - SCOPUS:0021966834
VL - 66
SP - 830
EP - 834
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -