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. 1980 May;77(5):2740–2742. doi: 10.1073/pnas.77.5.2740

Induction of differentiation of murine erythroleukemia cells by aminonucleoside of puromycin and inhibition of this induction by purines and purine derivatives.

F Lacour, L Harel, C Friend, T Huynh, J G Holland
PMCID: PMC349479  PMID: 6930663

Abstract

The effect of the aminonucleoside of puromycin (AMS) on Friend erythroleukemia cells in culture was investigated, because purines and purine analogues are known to act as inducers of differentiation. After treatment with 20-30 micro M AMS for 4 days, the cultures contained between 80 and 90% benzidine-positive cells. Stimulation of hemoglobin synthesis was dose and time dependent. Inosine had no stimulatory activity; however, when it was added to the medium together with AMS, erythroid differentiation was almost completely inhibited. The inhibitory effect of inosine on this potent inducer was also dose and time dependent. No cytotoxicity was observed with either compound, alone or in combination. Inhibition of AMS stimulation of erythroid differentiation was also observed in the presence of inosine monophosphate and poly(inosinic acid). Hypoxanthine had a dual effect. At high concentrations (500 microgram/ml) it acted as an inducer, but when added at low concentrations (20 microgram/ml) together with AMS it inhibited differentiation. These findings suggest there is a link between purine biosynthesis and the event(s) required to trigger differentiation. Agonist-antagonist activity of closely related biological compounds has thus been revealed in the erythroleukemia cells.

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Selected References

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

  1. Adesnik M., Snitkin H. Induction of erythroid differentiation in Friend leukemia cells by bromodeoxyuridine. J Cell Physiol. 1978 Jun;95(3):307–317. doi: 10.1002/jcp.1040950308. [DOI] [PubMed] [Google Scholar]
  2. Fontenelle L. J., Henderson J. F. An enzymatic basis for the inability of erythrocytes to synthesize purine ribonucleotides de novo. Biochim Biophys Acta. 1969 Feb 18;177(1):175–176. doi: 10.1016/0304-4165(69)90085-3. [DOI] [PubMed] [Google Scholar]
  3. Friedman E. A., Schildkraut C. L. Lengthening of the G1 phase is not strictly correlated with differentiation in Friend erythroleukemia cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3813–3817. doi: 10.1073/pnas.75.8.3813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gusella J. F., Housman D. Induction of erythroid differentiation in vitro by purines and purine analogues. Cell. 1976 Jun;8(2):263–269. doi: 10.1016/0092-8674(76)90010-6. [DOI] [PubMed] [Google Scholar]
  6. Krenitsky T. A., Elion G. B., Henderson A. M., Hitchings G. H. Inhibition of human purine nucleoside phosphorylase. Studies with intact erythrocytes and the purified enzyme. J Biol Chem. 1968 Jun 10;243(11):2876–2881. [PubMed] [Google Scholar]
  7. LOWY B. A., WILLIAMS M. K., LONDON I. M. Enzymatic deficiencies of purine nucleotide synthesis in the human erythrocyte. J Biol Chem. 1962 May;237:1622–1625. [PubMed] [Google Scholar]
  8. Orkin S. H., Harosi F. I., Leder P. Differentiation in erythroleukemic cells and their somatic hybrids. Proc Natl Acad Sci U S A. 1975 Jan;72(1):98–102. doi: 10.1073/pnas.72.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Reem G. H., Friend C. Purine metabolism in murine virus-induced erythroleukemic cells during differentiation in vitro. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1630–1634. doi: 10.1073/pnas.72.4.1630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Scher W., Preisler H. D., Friend C. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro. 3. Effects of 5-bromo-2'-deoxyuridine, dimethylformamide and dimethylsulfoxide. J Cell Physiol. 1973 Feb;81(1):63–70. doi: 10.1002/jcp.1040810108. [DOI] [PubMed] [Google Scholar]
  11. Studzinski G. P., Ellem K. A. Differences between diploid and heteroploid cultured mammalian cells in their response to puromycin aminonucleoside. Cancer Res. 1968 Sep;28(9):1773–1782. [PubMed] [Google Scholar]
  12. Terada M., Fried J., Nudel U., Rifkind R. A., Marks P. A. Transient inhibition of initiation of S-phase associated with dimethyl sulfoxide induction of murine erythroleukemia cells to erythroid differentiation. Proc Natl Acad Sci U S A. 1977 Jan;74(1):248–252. doi: 10.1073/pnas.74.1.248. [DOI] [PMC free article] [PubMed] [Google Scholar]

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