Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1975 Jul 1;66(1):128–144. doi: 10.1083/jcb.66.1.128

Inhibition by colchicine of the mitogenic stimulation of lymphocytes prior to the S phase

PMCID: PMC2109517  PMID: 1170172

Abstract

Colchicine, vinblastine, and vincristine inhibit the mitogenic stimulation of lymphocytes by concanavalin A as measured by the incorporation of [3H]thymidine and the appearance of blast cells. The inhibitory effect of colchicine could not be accounted for by diminution in cell viability or by metaphase arrest of mitosis in the stimulated cells. Moreover, the inhibition of [3H]thymidine incorporation was not due to blockage of thymidine transport or inhibition of DNA synthesis inasmuch as addition of colchicine had no effect on cells in the S phase of the cell cycle. The time of inhibition was correlated with the kinetics of cellular commitment to lectin activation and the kinetic data indicated that colchicine blocks stimulation early in the sequence of events following addition of the mitogen. These findings support the hypothesis that cytoplasmic microtubular function plays a role in the commitment of resting cells to undergo mitotic division.

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alford R. H. Metal cation requirements for phytohemagglutinin-induced transformation of human peripheral blood lymphocytes. J Immunol. 1970 Mar;104(3):698–703. [PubMed] [Google Scholar]
  2. Allan D., Michell R. H. Phosphatidylinositol cleavage in lymphocytes. Requirement for calcium ions at a low concentration and effects of other cations. Biochem J. 1974 Sep;142(3):599–604. doi: 10.1042/bj1420599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Allwood G., Asherson G. L., Davey M. J., Goodford P. J. The early uptake of radioactive calcium by human lymphocytes treated with phytohaemagglutinin. Immunology. 1971 Sep;21(3):509–516. [PMC free article] [PubMed] [Google Scholar]
  4. Andersson J., Edelman G. M., Möller G., Sjöberg O. Activation of B lymphocytes by locally concentrated concanavalin A. Eur J Immunol. 1972 Jun;2(3):233–235. doi: 10.1002/eji.1830020307. [DOI] [PubMed] [Google Scholar]
  5. Berlin R. D. Temperature dependence of nucleoside membrane transport of rabbit alveolar macrophages and polymorphonuclear leukocytes. J Biol Chem. 1973 Jul 10;248(13):4724–4730. [PubMed] [Google Scholar]
  6. Cunningham B. A., Wang J. L., Pflumm M. N., Edelman G. M. Isolation and proteolytic cleavage of the intact subunit of concanavalin A. Biochemistry. 1972 Aug 15;11(17):3233–3239. doi: 10.1021/bi00767a016. [DOI] [PubMed] [Google Scholar]
  7. Edelman G. M., Yahara I., Wang J. L. Receptor mobility and receptor-cytoplasmic interactions in lymphocytes. Proc Natl Acad Sci U S A. 1973 May;70(5):1442–1446. doi: 10.1073/pnas.70.5.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fisher D. B., Mueller G. C. An early alteration in the phospholipid metabolism of lymphocytes by phytohemagglutinin. Proc Natl Acad Sci U S A. 1968 Aug;60(4):1396–1402. doi: 10.1073/pnas.60.4.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fitzgerald P. H., Brehaut L. A. Depression of DNA synthesis and mitotic index by colchicine in cultured human lymphocytes. Exp Cell Res. 1970 Jan;59(1):27–31. doi: 10.1016/0014-4827(70)90619-1. [DOI] [PubMed] [Google Scholar]
  10. Gallin J. I., Rosenthal A. S. The regulatory role of divalent cations in human granulocyte chemotaxis. Evidence for an association between calcium exchanges and microtubule assembly. J Cell Biol. 1974 Sep;62(3):594–609. doi: 10.1083/jcb.62.3.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greaves M. F., Bauminger S. Activation of T and B lymphocytes by insoluble phytomitogens. Nat New Biol. 1972 Jan 19;235(55):67–70. doi: 10.1038/newbio235067a0. [DOI] [PubMed] [Google Scholar]
  12. Gunther G. R., Wang J. L., Edelman G. M. The kinetics of cellular commitment during stimulation of lymphocytes by lectins. J Cell Biol. 1974 Aug;62(2):366–377. doi: 10.1083/jcb.62.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gunther G. R., Wang J. L., Yahara I., Cunningham B. A., Edelman G. M. Concanavalin A derivatives with altered biological activities. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1012–1016. doi: 10.1073/pnas.70.4.1012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gustafsson M. K. Effect of colchicine on DNA synthesis in plerocercoids of Diphyllobothrium dendriticum (Cestoda). Exp Cell Res. 1968 Apr;50(1):1–8. doi: 10.1016/0014-4827(68)90387-x. [DOI] [PubMed] [Google Scholar]
  15. HELL E., COX D. G. Effects of colchicine and colchemid on synthesis of deoxyribonucleic acid in the skin of the guinea pig's ear in vitro. Nature. 1963 Jan 19;197:287–288. doi: 10.1038/197287a0. [DOI] [PubMed] [Google Scholar]
  16. Jasińska J., Steffen J. A., Michalowski A. Studies on in vitro lymphocyte proliferation in cultures synchronized by the inhibition of DNA synthesis. II. Kinetics of the initiation of the proliferative response. Exp Cell Res. 1970 Aug;61(2):333–341. doi: 10.1016/0014-4827(70)90455-6. [DOI] [PubMed] [Google Scholar]
  17. Kleinfeld R. G., Sisken J. E. Morphological and kinetic aspects of mitotic arrest by and recovery from colcemid. J Cell Biol. 1966 Dec;31(3):369–379. doi: 10.1083/jcb.31.3.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LA COUR L. F., PELC S. R. Effect of colchicine on the utilization of thymidine labelled with tritium during chromosomal reproduction. Nature. 1959 May 23;183(4673):1455–1456. doi: 10.1038/1831455a0. [DOI] [PubMed] [Google Scholar]
  19. Lacy P. E., Howell S. L., Young D. A., Fink C. J. New hypothesis of insulin secretion. Nature. 1968 Sep 14;219(5159):1177–1179. doi: 10.1038/2191177a0. [DOI] [PubMed] [Google Scholar]
  20. Lindahl-Kiessling K. Mechanism of phytohemagglutinin (PHA) action. V. PHA compared with concanavalin A (Con A). Exp Cell Res. 1972 Jan;70(1):17–26. doi: 10.1016/0014-4827(72)90176-0. [DOI] [PubMed] [Google Scholar]
  21. Lohrmann H. P., Graw C. M., Graw R. G., Jr Stimulated lymphocyte cultures: responder recruitment and cell cycle kinetics. J Exp Med. 1974 May 1;139(5):1037–1048. doi: 10.1084/jem.139.5.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Madoc-Jones H., Mauro F. Interphase action of vinblastine and vincristine: differences in their lethal action through the mitotic cycle of cultured mammalian cells. J Cell Physiol. 1968 Dec;72(3):185–196. doi: 10.1002/jcp.1040720306. [DOI] [PubMed] [Google Scholar]
  23. Maino V. C., Green N. M., Crumpton M. J. The role of calcium ions in initiating transformation of lymphocytes. Nature. 1974 Sep 27;251(5473):324–327. doi: 10.1038/251324b0. [DOI] [PubMed] [Google Scholar]
  24. McClain D. A., Wang J. L., Edelman G. M. The effects of sodium metaperiodate on T and B lymphocytes. Cell Immunol. 1975 Feb;15(2):287–293. doi: 10.1016/0008-8749(75)90007-6. [DOI] [PubMed] [Google Scholar]
  25. Medrano E., Piras R., Mordoh J. Effect of colchicine, vinblastine and cytochalasin B on human lymphocyte transformation by phytohemagglutinin. Exp Cell Res. 1974 Jun;86(2):295–300. doi: 10.1016/0014-4827(74)90716-2. [DOI] [PubMed] [Google Scholar]
  26. Mizel S. B., Wilson L. Nucleoside transport in mammalian cells. Inhibition by colchicine. Biochemistry. 1972 Jul 4;11(14):2573–2578. doi: 10.1021/bi00764a003. [DOI] [PubMed] [Google Scholar]
  27. PADAWER J. Effect of colchicine and related substances on the morphology of peritoneal mast cells. J Natl Cancer Inst. 1960 Oct;25:731–747. doi: 10.1093/jnci/25.4.731. [DOI] [PubMed] [Google Scholar]
  28. Powell A. E., Leon M. A. Reversible interaction of human lymphocytes with the mitogen concanavalin A. Exp Cell Res. 1970 Oct;62(2):315–325. doi: 10.1016/0014-4827(70)90560-4. [DOI] [PubMed] [Google Scholar]
  29. SELL S., GELL P. G. STUDIES ON RABBIT LYMPHOCYTES IN VITRO. I. STIMULATION OF BLAST TRANSFORMATION WITH AN ANTIALLOTYPE SERUM. J Exp Med. 1965 Aug 1;122:423–440. doi: 10.1084/jem.122.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sartorelli A. C., Creasey W. A. Cancer chemotherapy. Annu Rev Pharmacol. 1969;9:51–72. doi: 10.1146/annurev.pa.09.040169.000411. [DOI] [PubMed] [Google Scholar]
  31. Sasaki M. S., Norman A. Proliferation of human lymphocytes in culture. Nature. 1966 May 28;210(5039):913–914. doi: 10.1038/210913a0. [DOI] [PubMed] [Google Scholar]
  32. Steffen J. A., Stolzmann W. M. Studies on in vitro lymphocyte proliferation in cultures synchronized by the inhibition of DNA synthesis. I. Variability of S plus G2 periods of first generation cells. Exp Cell Res. 1969 Aug;56(2):453–460. doi: 10.1016/0014-4827(69)90039-1. [DOI] [PubMed] [Google Scholar]
  33. Sörén L. Variability of the time at which PHA-stimulated lymphocytes initiate DNA synthesis. Exp Cell Res. 1973 Mar 30;78(1):201–208. doi: 10.1016/0014-4827(73)90055-4. [DOI] [PubMed] [Google Scholar]
  34. TAYLOR E. W. THE MECHANISM OF COLCHICINE INHIBITION OF MITOSIS. I. KINETICS OF INHIBITION AND THE BINDING OF H3-COLCHICINE. J Cell Biol. 1965 Apr;25:SUPPL–SUPPL:160. doi: 10.1083/jcb.25.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wilson L., Bamburg J. R., Mizel S. B., Grisham L. M., Creswell K. M. Interaction of drugs with microtubule proteins. Fed Proc. 1974 Feb;33(2):158–166. [PubMed] [Google Scholar]
  36. Wilson L., Friedkin M. The biochemical events of mitosis. I. Synthesis and properties of colchicine labeled with tritium in its acetyl moiety. Biochemistry. 1966 Jul;5(7):2463–2468. doi: 10.1021/bi00871a042. [DOI] [PubMed] [Google Scholar]
  37. Yahara I., Edelman G. M. Electron microscopic analysis of the modulation of lymphocyte receptor mobility. Exp Cell Res. 1975 Mar 1;91(1):125–142. doi: 10.1016/0014-4827(75)90150-0. [DOI] [PubMed] [Google Scholar]
  38. Yahara I., Edelman G. M. Modulation of lymphocyte receptor redistribution by concanavalin A, anti-mitotic agents and alterations of pH. Nature. 1973 Nov 16;246(5429):152–155. doi: 10.1038/246152a0. [DOI] [PubMed] [Google Scholar]
  39. Yahara I., Edelman G. M. Restriction of the mobility of lymphocyte immunoglobulin receptors by concanavalin A. Proc Natl Acad Sci U S A. 1972 Mar;69(3):608–612. doi: 10.1073/pnas.69.3.608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Younkin L. H. In vitro response of lymphocytes to phytohemagglutinin (PHA) as studied with antiserum to PHA. I. Initiation period, daughter-cell proliferation, and restimulation. Exp Cell Res. 1972 Nov;75(1):1–10. doi: 10.1016/0014-4827(72)90512-5. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES