Differentiation of U937 cells induced by 5,8,11,14-eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism

Journal Article · Wed Nov 30 23:00:00 EST 1988 · Experimental Cell Research; (United States)

DOI:https://doi.org/10.1016/0014-4827(88)90285-6· OSTI ID:5267213

Ondrey, F; Anderson, K; Hoeltgen, D; Harris, J ^[1]

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1. Rush Medical College, Chicago, IL (USA)

5,8,11,14-Eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism, rapidly and reversibly inhibited DNA synthesis in U937 cells. This inhibition was not due to cytotoxicity, as judged by studies with trypan blue, release of {sup 51}Cr-labeled proteins, and its reversibility. When cells were cultured in the presence of ETYA for several days, morphologic, enzymatic, and functional changes consistent with differentiation occurred. The cells enlarged, the ratio of cytoplasm to nuclei increased, secretory granules and vacuoles developed, the apparent activity of nonspecific esterase rose, and ingestion of latex particles increased. A morphology consistent with that of an immature monocyte was evident by electron microscopy. When cells differentiated by ETYA were cultured in media free of the inhibitor, DNA synthesis reinitiated and the cell number increased; differentiation was phenotypic and not genotypic. To examine whether ETYA-induced differentiation was obligatorily related to its suppression of DNA synthesis, cells were incubated in 50 {mu}M hydroxyurea and DNA synthesis was inhibited for 24 to 36 h without morphologic evidence of cellular differentiation. However, addition of ETYA to cells prevented from dividing by hydroxyurea and subsequent culture for 72 h induced morphologic evidence of differentiation. The effects of ETYA on cell division and cell differentiation are closely related but can be dissociated.

• OSTI ID: 5267213
• Journal Information: Experimental Cell Research; (United States), Journal Name: Experimental Cell Research; (United States) Vol. 179:2; ISSN ECREA; ISSN 0014-4827
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
AMIDES
ARACHIDONIC ACID
AZINES
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CELL DIFFERENTIATION
CELL KILLING
CHROMIUM 51
CHROMIUM ISOTOPES
DAYS LIVING RADIOISOTOPES
DNA REPLICATION
EICOSANOIC ACID
ELECTRON CAPTURE RADIOISOTOPES
ENZYME INHIBITORS
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
HYDROXYUREA
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOTOPES
LEUKOCYTES
MATERIALS
METABOLISM
MOLECULAR BIOLOGY
MONOCARBOXYLIC ACIDS
MONOCYTES
MORPHOLOGY
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOTYPE
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
THYMIDINE
TRITIUM COMPOUNDS