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Cycloheximide protection against actinomycin D cytotoxicity
Author(s) -
Borrelli Michael J.,
Stafford Diane M.,
Rausch Cynthia M.,
Ofenstein John P.,
Cosenza Steven C.,
Soprano Kenneth J.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041530310
Subject(s) - cycloheximide , dactinomycin , biology , cytoplasm , messenger rna , microbiology and biotechnology , transcription (linguistics) , chinese hamster ovary cell , in vitro , protein biosynthesis , biochemistry , gene , linguistics , philosophy , receptor
Pretreatment plus concomitant treatment with 10 μg/ml cycloheximide protected Chinese hamster ovary cells and Swiss 3T3 cells against the cytotoxicity of actinomycin D. The cycloheximide treatment reduced the intracellular concentration of actinomycin D by reducing the level of actinomycin D bound to the acid precipitable fraction of the cell. Levels of unbound actinomycin D were unaffected by cycloheximide, indicating that the plasma membrane permeability to AD was not reduced. Actinomycin D inhibited total transcription but did not reduce cytoplasmic levels of rRNA nor of most tested mRNA; however, cytoplasmic levels of c‐myc mRNA were reduced below detectability. Cycloheximide treatment further inhibited total transcription and had no effect on cytoplasmic levels of rRNA nor of most tested mRNA. Cytoplasmic levels of c‐myc were elevated by cycloheximide and remained so even in the presence of actinomycin D. These data suggested that a reduction in cytoplasmic levels of short lived, essential mRNA, such as c‐myc mRNA, was one lethal lesion of actinomycin D. Furthermore, cycloheximide's protection may result, in part, from its ability to stabilize and/or elevate cytoplasmic levels of these mRNA, thus counteracting their depletion by actinomycin D. Protection may also result from the cycloheximide‐induced reduction of actinomycin D bound to the acid precipitable fraction of the cells. © 1992 Wiley‐Liss, Inc.