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Discrepancy between cytotoxicity, platinum accumulation, and DNA platination in MCF-7 breast cancer cells treated with diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and cisplatin

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Abstract

Cisplatin (cis), raceme-diaqua[1,2-bis(4-fluorophenyl)ethylenedi-amine]platinum(II) sulfate (r-4F-PtSO4), meso-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) sulfate (m-4F-PtSO4), and meso-diaqua[1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) sulfate (m-2,6Cl2-4OH-PtSO4) were compared with regard to their growth inhibitory effect on MCF-7 breast cancer cells. At concentrations of 5 μM, cis, r-4F-PtSO4, and m-4F-PtSO4 were essentially equiactive, whereas m-2,6Cl2-4OH-PtSO4 was ineffective. Platinum measurements by neutron activation analysis showed that a 24-h treatment of the MCF-7 cells with r-4F-PtSO4 and m-4F-PtSO4 caused a 22.3- and 10.3-fold accumulation, respectively, whereas the accumulation factors for cis (2.55) and m-2,6Cl2-4OH-PtSO4 (1.83) were very low. The comparison of DNA-associated platinum revealed a similar tendency. After 24 h of drug exposure, the base pair/platinum ratios were: 2.1·104 for r-4F-PtSO4, 3.7·104 for m-4F-PtSO4, 6.1·104 for cisplatin, and 8.1·104 for m-2,6Cl2-4OH-PtSO4. Thus, the grade of cytotoxicity was correlated neither with the extent of cellular platinum enrichment nor with the degree of genomic DNA platination.

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References

  1. R. Zeisler, F. Lux, H. Seidenberger, H. Schönenberger, and W. Beck, “Studies on the distribution of platinum in tumor-bearing rats after the administration of platinum coordination complexes used in cancer chemotherapy.” in:Nuclear Activation Techniques in the Life Sciences 1978. International Atomic Energy Agency, Wien (1979).

    Google Scholar 

  2. S. Trebert Haeberlin, F. Lux, J. Karl, T. Spruß, and H. Schönenberger,J. Radioanal. Nucl. Chem., Articles 113, 461 (1987).

    Article  Google Scholar 

  3. S. Trebert Haeberlin, F. Lux, T. Spruß, R. Gust, and H. Schönenberger, “Determination of platinum and biologically essential trace elements by neutron activation analysis in pharmacokinetic studies on cisplatin derivatives with estrophilic ligands.” in: M. Nicolini, ed.,Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy. Martinus Nijhoff Publishing, Boston (1988).

    Google Scholar 

  4. R. Müller, R. Gust, M. Jennerwein, H. Reile, R. Laske, W. Krischke, G. Bernhardt, Th. Spruss, J. Engel, and H. Schönenberger,Eur. J. Med. Chem. 24, 341 (1989).

    Article  Google Scholar 

  5. H. Reile, G. Bernhardt, M. Koch, H. Schönenberger, M. Hollstein, and F. Lux,Cancer Chemother. Pharmacol. 30, 113 (1992).

    Article  PubMed  CAS  Google Scholar 

  6. H. D. Soule, J. Vazques, A. Long, S. Albert, and M. Brennan,J. Natl. Cancer Inst. 51, 1409 (1973).

    PubMed  CAS  Google Scholar 

  7. R. J. Hay,Anal. Biochem. 187, 225 (1988).

    Article  Google Scholar 

  8. J. Karl, R. Gust, Th. Spruss, M. R. Schneider, H. Schönenberger, J. Engel K.-H. Wrobel, F. Lux, and S. Trebert Haeberlin,J. Med. Chem. 31, 72 (1988).

    Article  PubMed  CAS  Google Scholar 

  9. H. Reile, R. Müller, R. Gust, R. Laske, W. Krischke, G. Bernhardt, Th. Spruß, M. Jennerwein, J. Engel, S. Seeber, R. Osieka, and H. Schönenberger,Arch. Pharm. (Weinheim) 323, 133 (1990).

    Article  CAS  Google Scholar 

  10. H. Reile, Th. Spruß, R. Müller, R. Gust, G. Bernhardt, and H. Schönenberger,Arch. Pharm. (Weinheim) 323, 301 (1990).

    Article  CAS  Google Scholar 

  11. G. Bernhardt, H. Reile, Th. Spruß, M. Koch, R. Gust, H. Schönenberger, M. Hollstein, F. Lux, and J. Engel,Drugs of the Future 16, 899 (1991).

    Google Scholar 

  12. G. Bernhardt, H. Reile, H. Birnböck, Th. Spruß, and H. Schönenberger,J. Cancer Res. Clin. Oncol. 118, 35 (1992).

    Article  PubMed  CAS  Google Scholar 

  13. Th. Spruß, G. Bernhardt, E. Schickaneder, and H. Schönenberger,J. Cancer Res. Clin. Oncol. 117, 435 (1991).

    Article  PubMed  Google Scholar 

  14. F. M. Ausubel, R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, J. A. Smith, K. Struhl, eds.,Current Protocols, Greene and Wiley, New York (1993).

    Google Scholar 

  15. R. F. Boyer, inModern Experimental Biochemistry, Benjamin Cummings, Menlo Park, CA, pp. 437 and 479 (1986).

    Google Scholar 

  16. M. M. Bradford,Anal. Biochem. 72, 248 (1976).

    Article  PubMed  CAS  Google Scholar 

  17. P. A. Baedecker and W. D. Ehmann,Geochim. Cosmochim. Acta 29, 329 (1965).

    Article  CAS  Google Scholar 

  18. F. Lux, S. Trebert Haeberlin, W. Erhardt,Fresenius' Z. Anal. Chem. 323, 833 (1986).

    Article  CAS  Google Scholar 

  19. M. Hollstein, Dr. rer. nat. thesis, Technische Universität München, München (1996).

  20. F. E. Beamish, J. J. Russel, and J. Seath,Ind. Eng. Chem. Anal. Ed. 9, 174 (1937).

    Article  CAS  Google Scholar 

  21. R. Gijbels,Talanta 18, 587 (1971).

    Article  CAS  Google Scholar 

  22. R. A. Nadkarni and G. H. Morrison,Anal. Chem. 46, 232 (1974).

    Article  CAS  Google Scholar 

  23. A. Govaerts, R. Gijbels, and J. Hoste,Anal. Chim. Acta 79, 139 (1975).

    Article  CAS  Google Scholar 

  24. M. L. Verheijke,J. Radioanal. Chem. 35, 79 (1977).

    Article  CAS  Google Scholar 

  25. G. V. Veriovkin, E. N. Gilbert, and V. A. Mikhailov,J. Radioanal. Chem. 36, 359 (1977).

    Article  CAS  Google Scholar 

  26. J. Kucera and J. Drobnik,J. Radioanal. Chem. 75, 71 (1982).

    Article  CAS  Google Scholar 

  27. R. Zeisler and R. R. Greenberg,J. Radioanal. Chem. 75, 27 (1982).

    Article  CAS  Google Scholar 

  28. X. Lin, K. Heydorn, and B. Rietz,J. Radioanal. Chem., Articles 160, 85 (1992).

    Article  CAS  Google Scholar 

  29. D. Wildenhagen and V. Krivan,Anal. Chim. Acta 274, 257 (1993).

    Article  Google Scholar 

  30. F. Lux, M. Hollstein, H. Reile, G. Bernhardt, and H. Schönenberger,International Symposium on Instrumentalized Analytical Chemistry and Computer Technology, 14.–18. March, Düsseldorf, FRG (1994).

  31. M. Koch, Dr. rer. nat. thesis, Universität Regensburg, Regensburg (1993).

  32. E. Lindauer, Dr. rer. nat. thesis, Universität Regensburg, Regensburg (1994).

  33. B. D. Palmer, G. Wickham, D. J. Craik, W. D. McFadyen, L. P. G. Wakelin, B. C. Baguley, and W. A. Denny,Anti-Cancer Drug Design 7, 385 (1992).

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut für Radiochemie der Technischen Universität München, Walther-Meißner-Straße 3, D-85748, Garching, Germany

    Franz Lux & Michael Hollstein

  2. Institut für Pharmazie, Universität Regensburg, Universitätsstraße 31, D-93040, Regensburg, Germany

    Herta Reile, Günther Bernhardt & Helmut Schönenberger

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  1. Franz Lux
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  2. Michael Hollstein
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  3. Herta Reile
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  4. Günther Bernhardt
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  5. Helmut Schönenberger
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Lux, F., Hollstein, M., Reile, H. et al. Discrepancy between cytotoxicity, platinum accumulation, and DNA platination in MCF-7 breast cancer cells treated with diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and cisplatin. Biol Trace Elem Res 53, 113–128 (1996). https://doi.org/10.1007/BF02784549

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  • DOI: https://doi.org/10.1007/BF02784549

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