NDLI: Phorbol esters induce differentiation in human malignant T lymphoblasts.

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Phorbol esters induce differentiation in human malignant T lymphoblasts.

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Phorbol esters induce differentiation in human malignant T lymphoblasts.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nagasawa, K. Mak, T. W.
Abstract	At nanomolar concentrations, phorbol ester, a class of potent tumor promoters, can promote differentiation in the human malignant T-lymphoblastic cell line MOLT-3. The optimal dose for induction, as measured by the increase of the number of cells containing sheep erythrocyte receptors (E-rosette assay), is between 8 and 16 nM 12-O-tetradecanoylphorbol 13-acetate (TPA), although there were significant increases of E-rosette-positive (E(+)) cells at concentrations as low as 1.6 nM TPA. The induction was linear for 4 days, then it reached a plateau. This induction was independent of the cell densities of the cultures, and the viability of the E(+) cells remained high (95-100%) even after 10 days of culture in the presence of the tumor promoters. The E(+) cells, when measured with the more stable 2-aminoethylisothiouronium bromide E-rosette assay, indicated that virtually all (75-95%) of the MOLT-3 cells became E(+) by 4 days in culture. This induction by TPA was also accompanied by a dramatic drop in the plating efficiencies and a reduction in DNA synthesis. Examination of phorbol and other phrobol esters indicated that the ability to induce these cells correlated well with the tumor-promoting activities of these compounds, because only TPA and to a lesser extent phorbol 12,13,-dibenzoate induced E(+) cells, while phorbol and 4alpha-phorbol 12,13-didecanoate had no effect. Studies of MOLT-3 cells depleted of E(+) cells indicated that the induction of E(+) cells cannot be explained solely on the basis of enrichment or stimulation of the background E(+) cells in MOLT-3 cultures. Finally, we have shown that TPA also affected another differentiation marker, the loss of the enzyme terminal deoxyribonucleotidyl transferase. Terminal transferase activities and percentages of terminal-transferase-positive cells in these cultures were reduced to as low as 1/10th in 4 days in the presence of 16 nM TPA.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	77
Language	English
Publisher	National Academy of Sciences
Publisher Date	1980-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Leukemia, Experimental Pathology Phorbol Esters Pharmacology Phorbols T-Lymphocytes Cytology Animals Cell Differentiation Drug Effects Cell Division Cell Line DNA Nucleotidylexotransferase Metabolism Rosette Formation Enzymology Tetradecanoylphorbol Acetate Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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