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Metabolism, cellular actions, and cytotoxicity of selenomethionine in cultured cells

Abstract

Selenomethionine metabolism and the biochemical basis for its cytotoxicity were analyzed in cultured human and murine lymphoid cells. The metabolic pathways were also addressed, using purified mammalian enzymes and crude tissue extracts. Selenomethionine was found to be effectively metabolized toS-adenosylmethionine analog, and that analog was further metabolized in transmethylation reactions and in polyamine synthesis, similarly to the corresponding sulphur metabolites of methionine. Selenomethionine did not block these pathways, nor was there a specific block on the synthesis of DNA, RNA, or proteins when added to the culture medium. Selenomethionine showed cytotoxicity at above 40 μM levels. Yet, low selenomethionine levels (10 μM) could replace methionine and support cell growth in the absence of methionine. Selenomethionine toxicity took place concomitantly with changes inS-adenosylmethionine pools. D-form was less cytotoxic than L-form. Methionine concentration modified the cytotoxicity. Together, this indicates that selenomethionine uptake and enzymic metabolism are involved in the cytotoxicity in a yet unknown way.

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References

  1. 1.

    S. H. Mudd, and G. L. Cantoni,Nature 180, 1052 (1957).

  2. 2.

    J. R. Sufrin, J. B. Lombardini, D. L. Kramer, V. Alks, R. J. Bernachi, and C. W. Porter,Biological methylation and drug design, R. T. Borchartd, C. R. Creveling, and P. M. Ueland, eds., Humana, Clifton, NJ, pp. 373–384 (1986).

  3. 3.

    C. W. Porter, J. R. Sufrin, and D. D. Keith,Biochem. Biophys. Res. Comm. 122, 350 (1984).

  4. 4.

    S. J. Foster, R. J. Kraus, and H. E. Ganther,Arch. Biochem. Biophys. 251, 77 (1986).

  5. 5.

    J. L. Hoffman,Arch. Biochem. Biophys. 179, 136 (1977).

  6. 6.

    R. Cox,Proc. Am. Assoc. Cancer Res. 29, 8 (1984).

  7. 7.

    E. O. Kajander, M. Kubota, C. J. Carrera, J. A. Montgomery, and D. A. Carson,Cancer Res. 46, 2866 (1986).

  8. 8.

    M. Kantola, M. Saaranen, and T. Vanha-Perttula,J. Reprod. Fert. 83, 785 (1988).

  9. 9.

    D. A. Carson, J. Kaye, and J. E. Seegmiller,J. Immunol. 121, 1726 (1978).

  10. 10.

    R. J. Harvima, E. O. Kajander, I. T. Harvima, and J. E. Fräki,Biochim. Biophys. Acta 841, 42 (1985).

  11. 11.

    E. O. Kajander, and A. Raina,Biochem. J. 193, 503 (1981).

  12. 12.

    T. O. Eloranta, E. O. Kajander, and A. M. Raina,Biochem. J. 160, 287 (1976).

  13. 13.

    A. Raina, T. Hyvönen, T. Eloranta, M. Voutilainen, K. Samejima, and B. Yamanoha,Biochem. J. 219, 991 (1984).

  14. 14.

    A. Raina, R.-L. Pajula, and T. Eloranta,FEBS Lett. 67, 252 (1976).

  15. 15.

    E. O. Kajander, R.-L. Pajula, R. J. Harvima, and T. O. Eloranta,Anal. Biochem. 179, 396 (1989).

  16. 16.

    J. Wagner, C. Danzin, and P. Mamont,J. Chromatogr. 227, 349 (1982).

  17. 17.

    J. Parizek,Selenium in Biology and Medicine, Part A. G. R. Combs, Jr., J. E. Spallholz, O. A. Levander, and J. E. Oldfield, eds. Van Nostrand Reinhold, New York, pp. 66–77 (1987).

  18. 18.

    M. X. Sliwkowski,Methods Enzymol. 107, 620 (1984).

  19. 19.

    E. O. Kajander, L. Kauppinen, R. J. Harvima, S. O. Kärenlampi, and R. L. Pajula,Clin. Res. 36, 484A (1988).

  20. 20.

    D. C. German, C. A. Bloch, and N. M. Kredich,J. Biol. Chem. 258, 10997 (1983).

  21. 21.

    T. Iizasa, and D. A. Carson,Biochim. Biophys. Acta 844, 280 (1985).

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Author information

Correspondence to E. Olavi Kajander.

Additional information

This work was presented in the 4th International Symposium on Industrial Uses of Selenium and Tellurium, Banff, Alberta, Canada, May 7–10, 1989. It has not been published in the Proceedings of that symposium.

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Kajander, E.O., Harvima, R.J., Eloranta, T.O. et al. Metabolism, cellular actions, and cytotoxicity of selenomethionine in cultured cells. Biol Trace Elem Res 28, 57–68 (1991). https://doi.org/10.1007/BF02990463

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Keywords

  • SeMet
  • Selenomethionine
  • AdoMet
  • Polyamine Synthesis
  • Methionine Adenosyltransferase