Skip to main content
SpringerLink
Log in

Methylated oxypurines and induction of differentiation of murine erythroleukemia cells

  • Original Article
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Murine erythroleukemia cell lines derived from Friend virus infected mice can be induced to differentiate in vitro by numerous agents. Among these compounds are certain naturally occurring purines such as hypoxanthine or 1-methylhypoxanthine. We have extended these studies to other modified oxypurines and have identified some areas of cell regulation with which they may be interacting.

Monomethylated derivatives of guanine, hypoxanthine or xanthine are active as inducers of differentiation. Excluding hypoxanthine, the parent oxypurines guanine and xanthine are ineffective in inducing differentiation. The dimethyl- and trimethylxanthine derivatives are also inactive as inducers.

The methylated oxypurines are not metabolized to nucleotides by the cell and, therefore, probably do not interact with nucleic acid synthesis directly. We have investigated one cellular process of possible regulatory significance with which they do interact. ADP-ribosylation has been implicated in control of gene expression and differentiation. The methylated oxypurines inhibit this reaction, as measured in permeabilized cells, in the same concentration range at which they are effective as inducers of differentiation. Additionally, 1-methylguanine and 7-methylguanine decrease incorporation of mannose and glucosamine into glycoprotein and into dolichol-oligosaccharide precursors. These effects may be related to cell surface alterations observed during differentiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Waalkes TP, Borek E: The biochemical assessment of the malignant status in man: aspects related to tRNA modification. In: Excerpta Medica International Congress Series No. 375, pp. 15–31, Excerpta Medica, Amsterdam, 1975

    Google Scholar 

  2. Trewyn RW, Kerr SJ: Altered growth properties of Chinese hamster cells exposed to 1-methylguanine and 7-methylguanine. Cancer Res 38: 2285–2289, 1978

    Google Scholar 

  3. Trewyn RW, Lehman JM, Kerr SJ: Cell transformation by exogenous methylated purines. Adv Enzyme Regul 16: 335–345, 1978

    Google Scholar 

  4. Trewyn RW, Kerr SJ, Lehman JM: Karyotype and tumorigenicity of 1-methylguanine transformed Chinese hamster cells. J Natl Cancer Inst 62: 633–637, 1979

    Google Scholar 

  5. Kerr SJ: Induction of adipocyte formation in 10T1/2 cells by 1-methylguanine and 7-methylguanine. Tumour Biol 6: 115–121, 1985

    Google Scholar 

  6. Marks PA, Rifkind RA: Erythroleukemic differentiation. Annual Rev Biochem 47: 419–448, 1978

    Google Scholar 

  7. Lin T, Cheng J, Ishiguro K, Sartorelli AC: Purine and 8-substituted purine arabinofuranosyl and ribofuranosyl nucleoside derivatives as potential inducers of the differentiation of the Friend erythroleukemia. J Med Chem 28: 1481–1485, 1985

    Google Scholar 

  8. Kerr SJ: Induction of differentiation of Friend leukemia cells by purines and pyrimidines. Fed Proc 44: 314 Abs, 1985

    Google Scholar 

  9. Craddock VM, Mattocks AR, Magee PN: The fate of 7(14C)-methylguanine after administration to the rat. Biochem J 104: 74–78, 1968

    Google Scholar 

  10. Krenitsky TA, Elion GB, Henderson AM, Hitchings GH: Inhibition of human purine nucleoside phosphorylase. J Biol Chem 243: 2876–2881, 1968

    Google Scholar 

  11. Krenitsky TA, Papaioannou R, Elion GB: Human hypoxanthine phosphoribosyltransferase. J Biol Chem 244: 1263–1270, 1969

    Google Scholar 

  12. Shall S: ADP-ribosylation, DNA repair, cell differentiation and cancer in Proceedings of the 13th Princess Takamatsu Cancer Research Symposium (Eds O.H. Miwa, S. Shall and T. Sugimura) pp. 3–25 Japan Sci Soc Press, Tokyo/VNU Sci Press, Utrecht, 1983

  13. Terada M, Fujiki H, Marks PA, Sugimura T: Induction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds. Proc Natl Acad Sci USA 76: 6411–6414, 1979

    Google Scholar 

  14. Orkin SH, Harosi FI, Leder P: Differentiation in erythroleukemic cells and their somatic hybrids, Proc Natl Acad Sci USA 72: 98–102, 1975

    Google Scholar 

  15. Jacobson EL, Smith JY, Mingmwang M, Meadows R, Sims JL, Jacobson MK: Effect of nicotinamide analogues on recovery from DNA damage in C3H10T1/2 cells. Cancer Res 44: 2485–2492, 1984

    Google Scholar 

  16. Sokoloski JA, Blair OC, Sartorelli AC: Alterations in glycoprotein synthesis and guanosine triphosphate levels associated with the differentiation of HL-60 leukemia cells produced by inhibitors of inosine 5-phosphate dehydrogenase. Cancer Res 46: 2314–2319, 1986

    Google Scholar 

  17. Gusella JF, Housman D: Induction of erythroid differentiation in vitro by purines and purine analogues. Cell 8: 263–269, 1976

    Google Scholar 

  18. Gazitt Y, Reuben RC, Deitch AD, Marks PA, Rifkind RA: Changes in cyclic adenosine 3′:5′-monophosphate during induction of differentiation in murine erythroleukemia cells. Cancer Res 38: 3779–3783, 1978

    Google Scholar 

  19. Lucas DL, Webster HK, Wright DG: Purine metabolism in myeloid precursor cells during maturation. Studies with the HL-60 cell line. J Clin Invest 72: 1889–1900, 1983

    Google Scholar 

  20. Ishiguro K, Schwartz EL, Sartorelli AC: Characterization of the metabolic forms of 6-thioguanine responsible for cytotoxicity and induction of differentiation of HL-60 acute promyelocytic leukemia cells. J Cellular Physiol 121: 383–390, 1984

    Google Scholar 

  21. Mandel P, Okazaki H, Niedergang C: Poly (adenosine diphosphate ribose). Prog in Nuc Acid Res 27: 1–51, 1982

    Google Scholar 

  22. Durkacz BW, Omidiji O, Gray DA, Shall S: (ADP-ribose) participates in DNA excision repair. Nature 283: 593–596, 1980

    Google Scholar 

  23. Morioka K, Tanaka K, Nokuo T, Ishizawa M, Ono T: Erythroid differentiation and poly (ADP-ribose) synthesis in Friend leukemia cells. Gann 70: 37–46, 1979

    Google Scholar 

  24. Kerr SJ: Alterations in cell surface properties induced by modified purines. Tumour Biology 6: 123–131, 1985

    Google Scholar 

  25. Kerr SJ: Ribavirin induced differentiation of murine erythroleukemia cells. Mol Cell Biochem 77: 187–194, 1987

    Google Scholar 

  26. Gazitt Y, Deitch AD, Marks PA, Rifkind RA: Cell volume changes in relation to the cell cycle of differentiating erythroleukemic cells. Exp Cell Res 117: 413–420, 1978

    Google Scholar 

  27. Sartorelli AC: Malignant cell differentiation as a potential therapeutic approach. Br J Cancer 52: 293–302, 1985

    Google Scholar 

  28. Rowinsky EK, Ettinger DS, McGuire WP, Noe DA, Grochow LB, Donehower RC: Prolonged infusion of hexamethylene bisacetamide: A phase I and pharmacological study. Cancer Res 47: 5788–5795, 1987

    Google Scholar 

  29. Muralidhar G, Trewyn RW: Enhancement of the chemical transformation of Chinese hamster embryo cells in vitro by 7-methylguanine. Cancer Res 47: 2440–2444, 1987

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Biochemistry/Biophysics/Genetics, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, 80262, Denver, Colorado, USA

    Sylvia J. Kerr

Authors
  1. Sylvia J. Kerr
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kerr, S.J. Methylated oxypurines and induction of differentiation of murine erythroleukemia cells. Mol Cell Biochem 92, 37–44 (1990). https://doi.org/10.1007/BF00220717

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00220717

Key words

Search

Navigation