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On the differential cytotoxicity of actinomycin D.
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MedLine Citation:
PMID:  4398631     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Actinomycin D (AMD) at concentrations that inhibit cellular RNA synthesis by 85% or more causes an acute phase of lethal cell degeneration in HeLa cultures beginning as early as 3 hr after drug exposure, resulting in the nearly complete loss of viable cells by 12 hr. The loss of cells during this acute phase of lethality is closely dose dependent. Vero, WI38, or L cells are not susceptible to this early acute cyto-intoxication by AMD, and may begin to die only after 1-2 days. Differential susceptibility to acute cyto-intoxication by AMD, or other inhibitors of RNA synthesis (daunomycin or nogalamycin), among different types of cultured cells is analogous to that observed in vivo in certain tissues and tumors, and cannot be accounted for by differences in the effect of AMD on RNA, DNA, or protein syntheses, or by the over-all loss of preformed RNA. Actinomycin D in a dose that inhibits RNA synthesis causes an equivalent loss of the prelabeled RNA in all the cell types studied. Inhibition of protein synthesis with streptovitacin A or of DNA synthesis with hydroxyurea does not cause acute lethal injury in HeLa cells as does inhibition of RNA synthesis. Furthermore, since Vero or L cells divide at about the same rate as HeLa cells, no correlation can be drawn between the rate of cell proliferation and susceptibility to the cytotoxicity of AMD. Susceptibile cells are most vulnerable to intoxication by AMD in the G(1)-S interphase or early S phase. Inhibition of protein synthesis (which protects cells against damage by other agents affecting DNA) does not protect against AMD-induced injury. Although HeLa cells bind more AMD at a given dose than Vero or L cells, the latter cell types, given higher doses, can be made to bind proportionally more AMD without succumbing to acute cyto-intoxication. It is suggested that the differential susceptibility of these cell types to acute poisoning by AMD may reflect differences among various cells in the function or stability of certain RNA species not directly involved in translation whose presence is vital to cells. In HeLa cells, these critical species of RNA are presumed to have a short half-life.
Authors:
S G Sawicki; G C Godman
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of cell biology     Volume:  50     ISSN:  0021-9525     ISO Abbreviation:  J. Cell Biol.     Publication Date:  1971 Sep 
Date Detail:
Created Date:  1971-12-12     Completed Date:  1971-12-12     Revised Date:  2010-06-22    
Medline Journal Info:
Nlm Unique ID:  0375356     Medline TA:  J Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  746-61     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Carbon Isotopes
Cell Division / drug effects
Cell Line
Cell Survival / drug effects
Cells, Cultured / drug effects
Culture Techniques
DNA / antagonists & inhibitors,  biosynthesis
DNA, Neoplasm / antagonists & inhibitors,  biosynthesis
Dactinomycin / metabolism,  pharmacology*
Half-Life
Haplorhini
Hela Cells / metabolism
Humans
Hydroxyurea / pharmacology
Kidney
L Cells (Cell Line)
Lung
Methods
Mice
Protein Biosynthesis
Proteins / antagonists & inhibitors
RNA / antagonists & inhibitors,  biosynthesis
RNA, Neoplasm / antagonists & inhibitors,  biosynthesis
Streptovaricin / pharmacology
Time Factors
Uridine / metabolism
Chemical
Reg. No./Substance:
0/Carbon Isotopes; 0/DNA, Neoplasm; 0/Proteins; 0/RNA, Neoplasm; 127-07-1/Hydroxyurea; 1404-74-6/Streptovaricin; 50-76-0/Dactinomycin; 58-96-8/Uridine; 63231-63-0/RNA; 9007-49-2/DNA
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Full Text
Journal Information
Journal ID (nlm-ta): J Cell Biol
ISSN: 0021-9525
ISSN: 1540-8140
Publisher: The Rockefeller University Press
Article Information
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Copyright © 1971 by The Rockefeller University Press
Received Day: 4 Month: 12 Year: 1970
Revision Received Day: 14 Month: 1 Year: 1971
Print publication date: Day: 1 Month: 9 Year: 1971
Volume: 50 Issue: 3
First Page: 746 Last Page: 761
ID: 2108313
PubMed Id: 4398631

ON THE DIFFERENTIAL CYTOTOXICITY OF ACTINOMYCIN D
Stanley G. Sawicki
Gabriel C. Godman
From the Department of Pathology, Columbia University, New York 10032


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