Document Detail

Induction of murine teratocarcinoma cell differentiation by suppression of poly(ADP-ribose) synthesis.
MedLine Citation:
PMID:  6095269     Owner:  NLM     Status:  MEDLINE    
Poly(ADP-ribose) synthesizing activity in mouse teratocarcinoma EC-A1 cells decreased markedly during differentiation induced by retinoic acid; the activities assayed in permeabilized cells decreased to 25% and 10% of the activity of control (uninduced cells) 2 and 3 days, respectively, after the addition of 0.1 microM retinoic acid to the culture medium. This change preceded changes in morphology and DNA synthesis, which became prominent after 4 days. The decrease in poly(ADP-ribose) synthesizing activity appeared to be caused by a diminution of the synthetase protein and not by a decrease in its catalytic activity, because the full activity disclosed by DNase I treatment decreased in parallel, albeit at about 20 times higher levels. When 8 mM 3-aminobenzamide or 10 mM nicotinamide, specific inhibitors of poly(ADP-ribose) synthetase, was added to the culture medium, the cells underwent differentiation after 7-9 days. An analogue, 3-aminobenzoic acid, which is not inhibitory to the synthetase, induced differentiation much less efficiently than did 3-aminobenzamide, and the effect of 3-aminobenzoic acid appeared to be ascribable to its potent cytotoxicity. Immunohistochemical analysis using anti-poly(ADP-ribose) antibody confirmed the marked reduction in poly(ADP-ribose) synthesizing activity in nuclei of the cells treated with retinoic acid or 3-aminobenzamide but not with 3-aminobenzoic acid. These results suggest that a decrease in poly(ADP-ribose) synthesis triggers differentiation of teratocarcinoma cells.
Y Ohashi; K Ueda; O Hayaishi; K Ikai; O Niwa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  81     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1984 Nov 
Date Detail:
Created Date:  1985-01-02     Completed Date:  1985-01-02     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7132-6     Citation Subset:  IM    
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MeSH Terms
Aminobenzoic Acids / pharmacology
Benzamides / pharmacology
Cell Differentiation* / drug effects
Cell Division / drug effects
Cell Survival / drug effects
Cells, Cultured
DNA Replication / drug effects
NAD+ Nucleosidase / antagonists & inhibitors*
Poly(ADP-ribose) Polymerases / antagonists & inhibitors*,  metabolism
Teratoma / pathology*
Tretinoin / pharmacology*
Reg. No./Substance:
0/Aminobenzoic Acids; 0/Benzamides; 302-79-4/Tretinoin; 3544-24-9/3-aminobenzamide; EC Polymerases; EC Nucleosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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