Effect of thymosin and phorbol ester on purine metabolic enzymes and cell surface phenotype in a malignant T-cell line (MOLT-3).
Previous studies have shown that thymosin (fraction 5) is able to induce surface differentiation markers on normal murine bone marrow T-cell precursors. Phorbol ester (TPA) promotes differentiation of human leukaemic lymphoblasts as assessed by changes in phenotypic surface markers and terminal deoxynucleotidyl transferase (TdT) activity. Changes in levels of purine degradative enzymes occur during T-cell maturation with a fall in adenosine deaminase (ADA) and a rise in purine nucleoside phosphorylase (PNP) and 5'nucleotidase (5'NT) activities. We have now investigated the effect of both thymosin (fraction 5) and TPA on a human leukaemic T-cell line (MOLT-3) in expression of the surface antigenic markers NAI/34 (a marker of immature thymocytes) and OKT11 (which corresponds to the sheep erythrocyte receptor) and of TdT, ADA, PNP and 5'NT. Thymosin (after 96 h incubation) significantly reduced the number of cells positive for NAI/34 from 76.0 +/- 5.0% (mean +/- S.D.) to 51.3 +/- 9.3% (p less than 0.01) but caused no significant change in the percentage of TdT or OKT11 positive cells. ADA levels were significantly reduced (p less than 0.02) and 5'NT levels were significantly elevated (mean increase 303 +/- 142% of control, p less than 0.001) but the increase in PNP level (108 +/- 16.8% of control) was not significant (p greater than 0.05). On the other hand, TPA (after 96 h incubation) significantly reduced cells positive for NAI/34 from 76.0 +/- 5.0 to 30.0 +/- 9.8% and for TdT from 81.7 +/- 6.5 to 17.3 +/- 4.4% and increased OKT11 positive cells from 67.3 +/- 5.5 to 89.0 +/- 2.8% (p less than 0.001). TPA caused no significant change in 5'NT or ADA levels (p greater than 0.05), but an increase in PNP level to 158 +/- 12.9% of control (p less than 0.02). The present study demonstrates for the first time that the normal thymic hormone, thymosin is capable of inducing differentiation changes in thymic derived human leukaemic cells. In addition, it shows that different inducing agents may cause different patterns of differentiation changes in leukaemic cells.
D015720:5'-Nucleotidase; D000243:Adenosine Deaminase / Q000378:metabolism; D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D006801:Humans; D008940:Mitotic Index; D009708:Nucleotidases / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D010641:Phenotype; D010704:Phorbols / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013947:Thymosin / Q000494:pharmacology*
D000954:Antigens, Surface; D010704:Phorbols; D011687:Purines; D013947:Thymosin; D010430:Pentosyltransferases; D004253:DNA Nucleotidylexotransferase; D009708:Nucleotidases; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; D013755:Tetradecanoylphorbol Acetate