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Microcalorimetric evaluation of the effects of methotrexate and 6-thioguanine on sensitive T-lymphoma cells and on a methotrexate-resistant subline

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Abstract

Isothermal microcalorimetry was used in order to continuously monitor and quantitatively assess the action of two antineoplastic drugs, methotrexate (MTX) and 6-thioguanine (6-TG), on a human T-lymphoma cell line, CCRF-CEM. The results with MTX were compared with data from experiments with a MTX-resistant subline, CEM/MTX. The slope of the power-time curve after drug injection relative to that obtained during unperturbed growth, was used to construct dose-response curves. The normal cell line was characterized by aD 50 value (i.e., the dose producing half the maximal response) of 0.05 μM for MTX and 0.38 μM for 6-TG. For the MTX-resistant subline theD 50 value was 8 μM of MTX. Comparisons of the continuous power-time curves showed the inhibitory effect of 6-TG to be faster than that of MTX.

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References

  1. Bäckman, P., Kimura, T., Schön, A., and Wadsö, I. (1992) Effects of pH-variations on the kinetics of growth and energy metabolism in cultured T-lymphoma cells: a microcalorimetric study.J. Cell. Physiol. 150, 99–103.

    Article  PubMed  Google Scholar 

  2. Kemp, R. B. (1991) Calorimetric studies of heat flux in animal cells.Thermochim. Acta 193, 253–267.

    Article  Google Scholar 

  3. Borrebaeck, C. A. K., and Schön, A. (1987) Antiproliferative response of human leukemic cells: PHA induced inhibition of DNA-synthesis and cellular metabolism.Cancer Res. 47, 4345–4350.

    PubMed  CAS  Google Scholar 

  4. Schön, A. and Wadsö, I. (1988) The potential use of microcalorimetry in predictive tests of the action of antineoplastic drugs on mammalian cells.Cytobios. 55, 33–39.

    PubMed  Google Scholar 

  5. Kimura, T., Schön A., and Wadsö, I. (1990) Prediction of the cytotoxic effects of some antineoplastic drugs on cultured T-lymphoma cells.Cytobios. 63, 7–13.

    PubMed  CAS  Google Scholar 

  6. Armstrong, R. D., Vera, R., Snyder, P., and Cadman, E. (1982) Enhancement of 6-thioguanine cytotoxic activity with methotrexate.Biochem. Biophys. Res. Commun. 109, 595–601.

    Article  PubMed  CAS  Google Scholar 

  7. Jansen, G., Westerhof, G. R., Kathmann, I., Rademaker, B. C., Rijksen, G., and Schornagel, J. H. (1989) Identification of a membrane-associated folate binding protein in human leukemic CCRF-CEM cells with transport-related methotrexate resistance.Cancer Res. 49, 2455–2459.

    PubMed  CAS  Google Scholar 

  8. Martin, D. S. (1987) Purine and pyrimidine biochemistry, and some relevant clinical and preclinical cancer chemotherapy research, inMetabolism and Action of Anticancer Drugs, Powis, G. and Prough, R. A., eds., Taylor and Francis, London, UK, pp. 91–140.

    Google Scholar 

  9. Foley, G. E., Lazarus, H., Farber, S., Geren Uzman, B., Boone, B. A., and McCarthy, R. E. (1965) Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukemia.Cancer 18, 522–529.

    Article  PubMed  CAS  Google Scholar 

  10. Suurkuusk, J. and Wadsö, I. (1982) A multichannel microcalorimeter system.Chem. Scr. 20, 155–163.

    CAS  Google Scholar 

  11. Bäckman P. and Wadsö, I. (1991) Cell growth experiments using a microcalorimetric vessel equipped with oxygen and pH electrodes.J. Biochem. Biophys. Meth. 23, 283–293.

    Article  PubMed  Google Scholar 

  12. Görman Nordmark, M., Laynez, J., Schön, A., and Wadsö, I. (1984). Design and testing of a new microcalorimetric vessel for use with living cellular systems and in titration experiments.J. Biochem. Biophys. Meth. 10, 187–202.

    Article  Google Scholar 

  13. Lönnbro, P. and Wadsö, I. (1991) Effect of dimethyl sulphoxide and some antibiotics on cultured human T-lymphoma cells as measured by microcalorimetry.J. Biochem. Biophys. Meth. 22, 331–336.

    Article  PubMed  Google Scholar 

  14. Bäckman, P. (1990) Effects of experimental factors on the metabolic rate of T-lymphoma cells as measured by microcalorimetry.Thermochim. Acta 172, 123–130.

    Article  Google Scholar 

  15. Hill, B. T. and Baserga, R. (1975) The cell cycle and its significance for cancer treatment.Cancer Treat. Rev. 2, 159–175.

    Article  PubMed  CAS  Google Scholar 

  16. Rosowsky, A., Lazarus, H., Yuan, G. C., Beltz, W. R., Mangini, L., Abelson, H. T., Modest, E. J., and Frei, E., III (1980) Effects of methotrexate esters and other lipophilic antifolates on methotrexate-resistant human leukemic lymphoblasts.Biochem. Pharmacol. 29, 648–652.

    Article  PubMed  CAS  Google Scholar 

  17. Mini, E., Moroson, B. A., Franco, C. T., and Bertino, J. R. (1985) Cytotoxic effects of folate antagonists against methotrexate-resistant human leukemic lymphoblasts CCRF-CEM cell lines.Cancer Res. 5, 325–330.

    Google Scholar 

  18. Schön, A. and Wadsö, I. (1986) Thermochemical characterization of T-lymphoma cells under non-growing conditions.Cytobios. 48, 195–205.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Facultat d’Odontologia, Universitat de Barcelona, Feixa Llarga, E-08907 L’Hospitalet, Barcelona, Spain

    Jordi Bermudez

  2. Division of Thermochemistry, Chemical Center, University of Lund, PO Box 124, S-221 00, Lund, Sweden

    Per Bäckman & Arne Schön

Authors
  1. Jordi Bermudez
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  2. Per Bäckman
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  3. Arne Schön
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Bermudez, J., Bäckman, P. & Schön, A. Microcalorimetric evaluation of the effects of methotrexate and 6-thioguanine on sensitive T-lymphoma cells and on a methotrexate-resistant subline. Cell Biophysics 20, 111–123 (1992). https://doi.org/10.1007/BF02823653

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  • DOI: https://doi.org/10.1007/BF02823653

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