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Induction of apoptosis and c-myc in L1210 lymphocytic leukemia cells by adenosine

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Journal of Biomedical Science

Abstract

High concentrations of adenosine (Ado), when added to L1210 lymphocytic leukemia cells, resulted in apoptosis or programmed cell death. The apoptotic process was accompanied by distinct morphological changes including chromatin condensation and blebbing of plasma membranes. Extensive DNA fragmentation was correlated with Ado concentrations. Furthermore, apoptosis in these cells was preceded by an early but transient expression of c-myc proto-oncogene, and was not influenced by homocysteine thiolactone added to the cells. Since severe combined immunodeficiency (SCID) is associated with a deficiency of adenosine deaminase, leading to defects in both cellular and humoral immunity, Ado-induced apoptosis may thus be a contributing factor in the pathology of SCID.

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References

  1. Arends MJ, McGregor AH, Toft NJ, Brown EJH, Wyllie AH. Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha-ras oncogenes and is associated with endonuclease availability. Br J Cancer 68:1127–1133;1993.

    Google Scholar 

  2. Arends MJ, Morris RG, Wyllie AH. Apoptosis: The roles of the endonucleases. Am J Pathol 136:593–608;1990.

    Google Scholar 

  3. Bissonnette RP, Echeverri F, Mahboubi A, Green DR. Apoptotic cell death induced by c-myc is inhibited bybcl-2. Nature 359:552–554;1992.

    Google Scholar 

  4. Carson DA, Seegmiller JE. Effect of adenosine deaminase inhibition upon human lymphocyte blastogenesis. J Clin Invest 57:274–282;1976.

    Google Scholar 

  5. Chiang PK, Cantoni GL, Ray DA, Bader JP. Reduced levels of adenosine deaminase in chick embryo fibroblasts transformed by Rous sarcoma virus. Biochem Biophys Res Commun 78:336–342;1977.

    Google Scholar 

  6. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159;1987.

    Google Scholar 

  7. Donfrio J, Coleman MS, Hutton JJ, Daoud A, Lampkin B, Dyminski J. Overproduction of adenine deoxynucleosides and deoxynucleotides in adenosine deaminase deficiency with severe combined immunodeficiency disease. J Clin Invest 62:884–887;1978.

    Google Scholar 

  8. Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ, Hancock DC. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69:119–128;1992.

    Google Scholar 

  9. Garcia-Castro I, Mato JM, Vasanthakumar G, Wiesmann WP, Schiffmann E, Chiang PK. Paradoxical effects of adenosine on neutrophil chemotaxis. J Biol Chem 258:4345–4349;1983.

    Google Scholar 

  10. Green H, Chan TS. Pyrimidine starvation induced by adenosine in fibroblasts and lymphoid cells: Role of adenosine deaminase. Science 182:836–837;1973.

    Google Scholar 

  11. Hirschorn R, Roegner V. Plasma deoxyadenosine, adenosine, and erythrocyte deoxyATP are elevated at birth in an adenosine deaminase-deficient child. J Clin Invest 65:768–771;1980.

    Google Scholar 

  12. Katamatani N, Willis EH, Carson DA. Selection and characterization of a murine lymphoid cell line partially deficient in S-adenosylhomcysteine hydrolase. Biochem Biophys Acta 762:205–214;1983.

    Google Scholar 

  13. Kim IK, Lee JH, Sohn HW, Kim HS, Kim SH. Prostaglandin A2 and Δ12-prostaglandin J2 induce apoptosis in L1210 cells. FEBS Lett 321:209–214;1993.

    Google Scholar 

  14. Kredich NM, Hershfield MS. S-Adenosylhomocysteine toxicity in normal and adenosine kinase-deficient lymphoblasts of human origin. Proc Natl Acad Sci USA 76:2450–2454;1979.

    Google Scholar 

  15. Kredich NM, Martin DW Jr. Role of S-adeno-sylhomocysteine in adenosine-mediated toxicity in cultured mouse T lymphoma cells. Cell 12:931–938;1977.

    Google Scholar 

  16. Leonard EJ, Skeel A, Chiang PK, Cantoni GL. The action of the adenosylhomocysteine hydrolase inhibitor, 3-deazaadenosine, on phagocytic function of mouse macrophages and human monocytes. Biochem Biophys Res Commun 84:102–109;1978.

    Google Scholar 

  17. Lotem J, Sachs L. Regulation bybcl-2, c-myc and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation competent and defective myeloid leukemic cells. Cell Growth Differ 4:41–47;1993.

    Google Scholar 

  18. Mills GC, Schmalstieg FC, Trimmer KB, Goldman AS, Goldblum RM. Purine metabolism in adenosine deaminase deficiency. Proc Natl Acad Sci USA 73:2867–2871;1976.

    Google Scholar 

  19. Porat N, Gill D, Parola AH. Adenosine deaminase in cell transformation: Biophysical manifestation of membrane dynamics. J Biol Chem 263:14608–14611;1988.

    Google Scholar 

  20. Shi Y, Glynn JM, Guilbert LJ, Cotter TG, Bissonnette RP, Green DR. Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science 257:212–214;1992.

    Google Scholar 

  21. Shipman C Jr, Drach JC. Absence of adenosine deaminase activity in a mammalian cell line transformed by Rous sarcoma virus. Science 200:1163–1165;1978.

    Google Scholar 

  22. Smeyne RJ, Vendrell M, Hayward M, Baker SJ, Miao GG, Schilling K, Robertson LM, Curran T, Morgan JI. Continuous c-fos expression precedes programmed cell death in vivo. Nature 363:166–169;1993.

    Google Scholar 

  23. Van der Weyden MB, Kelly WN. Adenosine deaminase deficiency and severe combined immunodeficiency disease. Life Sci 20:1645–1650;1977.

    Google Scholar 

  24. Wolberg G, Zimmerman TP, Hiemstra K, Winston M, Chu LC. Adenosine inhibition of lymphocyte-mediated cytolysis: Possible role of cyclic adenosine monophosphate. Science 1987:957–959;1975.

    Google Scholar 

  25. Wyllie AH, Arends MJ, Morris RG, Walker SW, Evan G. The apoptosis endonuclease and its regulation. Semin Immunol 4:389–397;1992.

    Google Scholar 

  26. Wyllie AH, Kerr JFR, Currie AR. Cell death: The significance of apoptosis. Int Rev Cytol 68:251–306;1980.

    Google Scholar 

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Kim, I.K., Copeland, R.L., Lee, J.H. et al. Induction of apoptosis and c-myc in L1210 lymphocytic leukemia cells by adenosine. J Biomed Sci 1, 154–157 (1994). https://doi.org/10.1007/BF02253342

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  • DOI: https://doi.org/10.1007/BF02253342

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