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
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