Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1987 Mar 1;242(2):479–483. doi: 10.1042/bj2420479

Effect of alpha-difluoromethylornithine on DNA methylation in murine erythroleukaemic cells. Relationship to stimulation of induced differentiation.

P Papazafiri, H B Osborne
PMCID: PMC1147730  PMID: 3109392

Abstract

Murine erythroleukaemic (MEL) cells cultured with alpha-difluoromethylornithine (DFMO) accumulated decarboxylated S-adenosylmethionine(decarboxylated AdoMet). In the absence of the inducer hexamethylenebisacetamide (HMBA), this accumulation of decarboxylated AdoMet was associated with a concomitant and proportional increase in DNA hypomethylation. In the presence of HMBA, DFMO, which stimulates the erythrodifferentiation of MEL cells, enhanced the differentiation-associated DNA hypomethylation. However, this differentiation-associated DNA hypomethylation was neither temporally nor quantitatively correlated with the accumulation of decarboxylated AdoMet in these cells. Therefore DFMO probably stimulates the HMBA-induced differentiation of MEL cells and the associated DNA hypomethylation via the effect of this drug on polyamine biosynthesis.

Full text

PDF
479

Selected References

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

  1. Bestor T. H., Hellewell S. B., Ingram V. M. Differentiation of two mouse cell lines is associated with hypomethylation of their genomes. Mol Cell Biol. 1984 Sep;4(9):1800–1806. doi: 10.1128/mcb.4.9.1800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bestor T. H., Ingram V. M. Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5559–5563. doi: 10.1073/pnas.80.18.5559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen K. Y., Nau D., Liu A. Y. Effects of inhibitors of ornithine decarboxylase on the differentiation of mouse neuroblastoma cells. Cancer Res. 1983 Jun;43(6):2812–2818. [PubMed] [Google Scholar]
  4. Christman J. K., Price P., Pedrinan L., Acs G. Correlation between hypomethylation of DNA and expression of globin genes in Friend erythroleukemia cells. Eur J Biochem. 1977 Nov 15;81(1):53–61. doi: 10.1111/j.1432-1033.1977.tb11926.x. [DOI] [PubMed] [Google Scholar]
  5. Davis T., Rinaldi A., Clark L., Adams R. L. Methylation of chromatin in vitro. Biochim Biophys Acta. 1986 May 5;866(4):233–241. doi: 10.1016/0167-4781(86)90048-5. [DOI] [PubMed] [Google Scholar]
  6. Käpyaho K., Jänne J. Stimulation of melanotic expression in murine melanoma cells exposed to polyamine antimetabolites. Biochem Biophys Res Commun. 1983 May 31;113(1):18–23. doi: 10.1016/0006-291x(83)90425-4. [DOI] [PubMed] [Google Scholar]
  7. Mamont P. S., Danzin C., Wagner J., Siat M., Joder-Ohlenbusch A. M., Claverie N. Accumulation of decarboxylated S-adenosyl-L-methionine in mammalian cells as a consequence of the inhibition of putrescine biosynthesis. Eur J Biochem. 1982 Apr;123(3):499–504. doi: 10.1111/j.1432-1033.1982.tb06559.x. [DOI] [PubMed] [Google Scholar]
  8. Meilhoc E., Moutin M. J., Osborne H. B. Catabolites produced by the deacetylation of hexamethylenebisacetamide play a key role in murine erythroleukaemic-cell differentiation. Biochem J. 1986 Sep 15;238(3):701–707. doi: 10.1042/bj2380701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Meilhoc E., Moutin M. J., Romani B. H., Osborne H. B. Relationship between ornithine decarboxylase activity and hexamethylene bisacetamide-induced differentiation of murine erythroleukemia cells. Exp Cell Res. 1986 Jan;162(1):142–150. doi: 10.1016/0014-4827(86)90432-5. [DOI] [PubMed] [Google Scholar]
  10. Oredsson S. M., Billgren M., Heby O. Induction of F9 embryonal carcinoma cell differentiation by inhibition of polyamine synthesis. Eur J Cell Biol. 1985 Sep;38(2):335–343. [PubMed] [Google Scholar]
  11. Osborne H. B., Bakke A. C., Yu J. Effect of dexamethasone on hexamethylene bisacetamide-induced Friend cell erythrodifferentiation. Cancer Res. 1982 Feb;42(2):513–518. [PubMed] [Google Scholar]
  12. Pegg A. E., McCann P. P. Polyamine metabolism and function. Am J Physiol. 1982 Nov;243(5):C212–C221. doi: 10.1152/ajpcell.1982.243.5.C212. [DOI] [PubMed] [Google Scholar]
  13. Pegg A. E., Pösö H., Shuttleworth K., Bennett R. A. Effect of inhibition of polyamine synthesis on the content of decarboxylated S-adenosylmethionine. Biochem J. 1982 Feb 15;202(2):519–526. doi: 10.1042/bj2020519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pegg A. E., Wechter R. S., Clark R. S., Wiest L., Erwin B. G. Acetylation of decarboxylated S-adenosylmethionine by mammalian cells. Biochemistry. 1986 Jan 28;25(2):379–384. doi: 10.1021/bi00350a016. [DOI] [PubMed] [Google Scholar]
  15. Schindler J., Kelly M., McCann P. P. The response of several murine embryonal carcinoma cell lines to stimulation of differentiation by alpha-difluoromethylornithine. J Cell Physiol. 1985 Jan;122(1):1–6. doi: 10.1002/jcp.1041220102. [DOI] [PubMed] [Google Scholar]
  16. Seiler N., Knödgen B. High-performance liquid chromatographic procedure for the simultaneous determination of the natural polyamines and their monoacetyl derivatives. J Chromatogr. 1980 Dec 12;221(2):227–235. doi: 10.1016/s0378-4347(00)84307-8. [DOI] [PubMed] [Google Scholar]
  17. Wagner J., Danzin C., Mamont P. Reversed-phase ion-pair liquid chromatographic procedure for the simultaneous analysis of S-adenosylmethionine, its metabolites and the natural polyamines. J Chromatogr. 1982 Feb 12;227(2):349–368. doi: 10.1016/s0378-4347(00)80389-8. [DOI] [PubMed] [Google Scholar]
  18. Wagner J., Hirth Y., Piriou F., Zakett D., Claverie N., Danzin C. N-Acetyl decarboxylated S-adenosylmethionine, a new metabolite of decarboxylated S-adenosylmethionine: isolation and characterization. Biochem Biophys Res Commun. 1985 Dec 17;133(2):546–553. doi: 10.1016/0006-291x(85)90941-6. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES