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PMID: 269404 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Tumor promoters inhibit spontaneous and induced differentiation of murine erythroleukemia cells in culture.

Yamasaki H, Fibach E, Nudel U, Weinstein IB, Rifkind RA, Marks PA

Abstract

Addition of the potent tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), to murine erythroleukemia cell lines in suspension cultures inhibited both spontaneous differentiation and differentiation induced by hexamethylene bisacetamide (HMBA), dimethyl sulfoxide, or butyric acid. Inhibition was unrelated to cytotoxicity and was reversible. When several plant diterpenes were tested, there was a positive correlation between tumor-promoting activity and inhibition of differentiation. TPA inhibited HMBA-induced differentiation only if added prior to the time of commitment to differentiation, as assayed by scoring for differentiation after transfer of cells from HMBA to fresh medium without HMBA. TPA-mediated inhibition of differentiation was associated with a decrease in globin mRNA accumulation.

MeSH Terms
Acetamides/pharmacology Animals Carcinogens/pharmacology Cell Differentiation/drug effects Cell Division/drug effects Cell Line Diamines/pharmacology Dose-Response Relationship, Drug Globins/biosynthesis Leukemia, Experimental/physiopathology Mice Nucleic Acid Hybridization Phorbol Esters/pharmacology RNA, Messenger/metabolism Tetradecanoylphorbol Acetate/pharmacology
Chemicals
Acetamides Carcinogens Diamines Phorbol Esters RNA, Messenger Globins hexamethylene bisacetamide Tetradecanoylphorbol Acetate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Yamasaki H
Fibach E
Nudel U
Weinstein I B
Rifkind R A
Marks P A
References (28)
28 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1977-08-00
Pages
3451-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC431603
Subset
IM
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