Advertisement

Methylthioadenosine (MeSAdo) Phosphorylase Deficiency in Malignancy

  • Dennis A. Carson
  • Tsutomu Nobori
  • E. Olavi Kajander
  • Carlos J. Carrera
  • Masaru Kubota
  • Hisashi Yamanaka
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)

Abstract

The abnormal growth properties of cancer cells must be mediated finally by changes in specific metabolic pathways. In general, malignant transformation is associated with an increase in the activities of enzymes involved in DNA, RNA, and protein synthesis, and a concomitant decrease in the activities of enzymes that degrade cellular metabolites. However, no specific metabolic pathway has been found that distinguishes normal from malignant cells, or is common to all tumors.

Keywords

Ornithine Decarboxylase Diphtheria Toxin Polyamine Metabolism Polyamine Synthesis Specific Metabolic Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J. I. Toohey, Methylthio group cleavage from methylthioadenosine. Description of an enzyme and its relationship to the methylthiorequirement of certain cells in culture, Biochem.Biophys.Res.Commun. 78: 1273 (1977).PubMedCrossRefGoogle Scholar
  2. 2.
    R-L. Pajula, and A. Raina, Methylthioadenosine, a potent inhibitor of spermine synthase from rat brain, FEBS Lett. 99: 343 (1979).PubMedCrossRefGoogle Scholar
  3. 3.
    H. G. Williams-Ashman, J. Seidenfeld, and P. Galletti, Trends in the biochemical pharmacology of 5′-deoxy-5′-methylthioadenosine, Biochem.Pharmacol. 31: 277 (1982).PubMedCrossRefGoogle Scholar
  4. 4.
    N. Kamatani, W. A. Nelson-Rees, and D. A. Carson, Selective killing of human malignant tumor cells deficient in methylthioadenosine phosphorylase, a purine metabolic enzyme, Proc.Natl.Acad.Sci.USA 78: 1219 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    N. Kamatani, A. L. Yu, and D. A. Carson, Deficiency of methylthioadenosine phosphorylase in human leukemic cells in vivo, Blood 60: 1387 (1982).PubMedGoogle Scholar
  6. 6.
    C. J. Carrera, R. L. Eddy, T. B. Shows, and D. A. Carson, Assignment of the gene for methylthioadenosine phosphorylase to human chromosome 9 by mouse-human somatic cell hybridization, Proc.Natl.Acad.Sci.USA 81: 2665 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    R. R. Chilcote, E. Brown, and J. D. Rowley, Lymphoblastic leukemia with lymphomatous features associated with abnormalities of the short arm of chromosome 9, N.Engl.J.Med. 313: 286 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    M. Kubota, N. Kamatani, and D. A. Carson, Biochemical genetic analysis of the role of methylthioadenosine phosphorylase in a murine lymphoid cell line, J.Biol.Chem. 258: 7288 (1983).PubMedGoogle Scholar
  9. 9.
    T. Iizasa, and D. A. Carson, Differential regulation of polyamine synthesis and transmethylation reactions in methylthioadenosine phosphorylase deficient mammalian cells, Biochim.Biophys.Acta 844: 280 (1985).PubMedCrossRefGoogle Scholar
  10. 10.
    A. E. Pegg, and P. P. McCann, Polyamine metabolism and function, Am.J.Phvsiol. 243: C212 (1982).Google Scholar
  11. 11.
    M. Kubota, E. O. Kajander, and D. A. Carson, Independent regulation of ornithine decarboxylase and S-adenosylmethionine decarboxylase in methylthioadenosine phosphorylase-deficient malignant murine lymphoblasts, Cancer Res. 45: 3567 (1985).PubMedGoogle Scholar
  12. 12.
    E. O. Kajander, M. Kubota, C. J. Carrera, J. A. Montgomery, and D. A. Carson, Resistance to multiple adenine nucleoside and methionine analogs in mutant lymphoma cells with enlarged S-adenosylmethionine pools, Cancer Res. 46: 2866 (1986).PubMedGoogle Scholar
  13. 13.
    H. Yamanaka, E. O. Kajander, and D. A. Carson, Modulation of diphthamide synthesis by 5′-deoxy-5′-methylthioadenosine in murine lymphoma cells, Biochim.Biophys.Acta 888: 157 (1986).PubMedCrossRefGoogle Scholar
  14. 14.
    H. Yamanaka, M. Kubota, and D. A. Carson, Synergistic inhibition of polyamine synthesis and growth by difluoromethylornithine plus methylthioadenosine in methylthioadenosine phosphorylase-deficient murine lymphoma cells, Cancer Res. 47: 1771 (1987).PubMedGoogle Scholar
  15. 15.
    D. A. Carson, E. H. Willis, and N. Kamatani, Metabolism to methionine and growth stimulation by 5′-methy1thioadenosine and 5′-methylthioinosine in mammalian cells, Biochem.Biophys.Res.Commun. 112: 391 (1983).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Dennis A. Carson
    • 1
  • Tsutomu Nobori
    • 1
  • E. Olavi Kajander
    • 1
  • Carlos J. Carrera
    • 1
  • Masaru Kubota
    • 1
  • Hisashi Yamanaka
    • 1
  1. 1.Department of Basic and Clinical ResearchResearch Institute of Scripps ClinicLa JollaUSA

Personalised recommendations