In Vitro

, Volume 20, Issue 8, pp 663–670 | Cite as

Elevated overall rates of transmethylation in cell lines from diverse human tumors

  • Peter H. Stern
  • Robert M. Hoffman
Rapid Communications

Summary

In a study of a diverse set of human tumor cell lines previously shown to all have a defect in methionine metabolism (Stern, P. H., Wallace, C. D. and Hoffman, R. M. J. Cellular Physiology119, 29–34, 1984), we demonstrate in this report that all have enhanced overall rates of transmethylation compared to normal human fibroblasts. Transmethylation rates were measured by blocking S-adenosylhomocysteine hydrolase and measuring the AdoHcy which accumulates as a result of transmethylation. The enhanced transmethylation rates may be the basis of the above-mentioned defects in methionine metabolism previously reported in human tumor cells, including the basis of the inability of the majority of the tumor cells to grow when methionine is replaced by homocysteine. The excess and unbalanced tRNA methylation observed for the last 25 years in many types of cancer may be at least in part explained by our results of elevated rates of overall transmethylation in cancer cells. The alteration of such a fundamental process as transmethylation in cancer may be indicative of its importance in the oncogenic process.

Key words

S-adenosylhomocysteine S-adenosylmethionine oxidized 3-deazaadenosine methionine dependence 

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References

  1. 1.
    Hoffman, R. M. (1982) In Vitro18, 421–428.PubMedGoogle Scholar
  2. 2.
    Mecham, J. O., Rowitch, D., Wallace, C. D., Stern, P. H. and Hoffman, R. M. (1983) Biochem. Biophys. Res. Commun.117, 429–434.PubMedCrossRefGoogle Scholar
  3. 3.
    Coalson, D. W., Mecham, J. O., Stern, P. H. and Hoffman, R. M. (1982) Proc. Natl. Acad. Sci. USA79, 4248–4251.PubMedCrossRefGoogle Scholar
  4. 4.
    Stern, P. H., Mecham, J. O., Wallace, C. D. and Hoffman, R. M. (1983) J. Cellular Physiology117, 9–14.CrossRefGoogle Scholar
  5. 5.
    Stern, P. H., Wallace, C. D. and Hoffman, R. M. (1984) J. Cellular Physiology119, 29–34.CrossRefGoogle Scholar
  6. 6.
    Baernstein H. D. (1934) J. Biol. Chem.106, 451–456.Google Scholar
  7. 7.
    Stern, P. H.; Mecham, J. O. and Hoffman, R. M. (1982) J. Biochem. & Biophys. Methods7, 83–88.CrossRefGoogle Scholar
  8. 8.
    Hoffman, J. L. (1979) In: Transmethylation (Usdin, E., Borchardt, R. T. and Creveling, C. R., eds.), Elsevier/North Holland, New York, 181–186.Google Scholar
  9. 9.
    Guranowski, A., Montgomery, J. A., Cantoni, G. I. and Chiang, P. K. (1981) Biochemistry20, 110–115.PubMedCrossRefGoogle Scholar
  10. 10.
    Johnson, G. S. and Chiang, P. K. (1981) Arch. Biochem. Biophys.210, 263–269.PubMedCrossRefGoogle Scholar
  11. 11.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. (1951) J. Biol. Chem.193, 265–275.PubMedGoogle Scholar
  12. 12.
    Hoffman, J. L. (1980) Arch. Biochem. Biophys.205, 132–135.PubMedCrossRefGoogle Scholar
  13. 13.
    Cory, J. G. and Mansell, M. M. (1975) Canc. Res.35, 390–396.Google Scholar
  14. 14.
    Tisdale, M. J. (1980) Biochim. Biophys. Acta.609, 296–305.PubMedGoogle Scholar
  15. 15.
    Borek, E., Gehrke, C. and Waalkes, T. (1979) In: Transmethylation (Usdin, E., Borchardt, R. and Creveling, C., eds.), Elsevier/North Holland, New York, 457–464.Google Scholar
  16. 16.
    Diala, E. S., Cheah, M. S. C., Rowitch, D. and Hoffman, R. M. (1983) J. Natl. Canc. Inst.71, 755–764.Google Scholar
  17. 17.
    German, D. C., Bloch, C. A. and Kredich, N. M. (1983) J. Biol. Chem.258, 10997–11003.PubMedGoogle Scholar
  18. 18.
    Pulciani, S., Santos, E., Lauver, A. V., Long, S. K., Robbins, K. C. and Barbacid, M. (1982) Proc. Natl. Acad. Sci. USA79, 2845–2849.PubMedCrossRefGoogle Scholar
  19. 19.
    Kaighn, M., Narayan, K. S., Ohnuki, Y., Lechner, J. and Jones, L. W. (1979) Invest. Urol.17, 16–23.PubMedGoogle Scholar
  20. 20.
    Fogh, J. (1978) Natl. Canc. Inst. Monogr.49, 5–9.Google Scholar
  21. 21.
    Soule, H. D., Vazquez, J., Long, A., Albert, S. and Brennan, M. (1973) J. Natl. Canc. Inst.51, 1409–1416.Google Scholar
  22. 22.
    Giard, D. J., Aaronson, S. A., Todaro, G. J., et al. (1973) J. Natl. Canc. Inst.51, 1417–1423.Google Scholar
  23. 23.
    Fogh, J. and Trempe, G. (1975) In: Human Tumor Cell LinesIn Vitro, J. Fogh, ed., Plenum Press, New York, 115–159.Google Scholar
  24. 24.
    Bubenik, J., Baresova, M., Viklicky, V., Jakoubkova, J., Sainerova, H. and Donner, J. (1973) Int. J. Cancer11, 765–773.PubMedCrossRefGoogle Scholar
  25. 25.
    Mickey, D., Stone, K. R., Wunderli, H., Mickey, G. H., Vollmer, R. T. and Paulson, D. F. (1977) Cancer Res.37, 4049–4058.PubMedGoogle Scholar
  26. 26.
    Aaronson, S. A., Todaro, G. J. and Freeman, A. E. (1970) Exp. Cell Res.61, 1–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Rasheed, S., Nelson-Rees, W. A., Toth, E. M. et al. (1974) Cancer33, 1027–1033.PubMedCrossRefGoogle Scholar
  28. 28.
    Eva, A., Robbins, K. C., Anderson, P. R., Srinivasan, A., Tronick, S., Reddy, E. P., Ellmore, N. W., Galen, A., Lautenberger, J., Papas, T. S., Westin, E., Wong-Staal, F., Gallo, R. C. and Aaronson, S. A. (1982) Nature295, 116–119.PubMedCrossRefGoogle Scholar
  29. 29.
    Fogh, J., Wright, W., and Loveless, J. (1977) J. Natl. Canc. Inst.58, 209–213.Google Scholar
  30. 30.
    Biedler, J. L., Helson, L. and Spengler, B. A. (1973) Cancer Res.33, 2643–2652.PubMedGoogle Scholar
  31. 31.
    Hoffman, R. M. (1984) Biochimica et Biophysica Acta Reviews on Cancer,738, 49–87.CrossRefGoogle Scholar
  32. 32.
    Nass, G., ed. 1983.Recent Results in Cancer Research, Vol. 84. Springer-Verlag, Berlin.Google Scholar

Copyright information

© Tissue Culture Association, Inc 1984

Authors and Affiliations

  • Peter H. Stern
    • 1
  • Robert M. Hoffman
    • 1
  1. 1.Department of Pediatrics, M-009University of California, San DiegoLa Jolla

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