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The cytotoxicity of T-2 toxin and related 12,13-epoxytrichothecenes to Adriamycin-sensitive and-resistant P388 leukemia cells

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The cytotoxicity of T-2 toxin and related trichothecenes was studied in Adriamycin-sensitive and-resistant P388 leukemia cells in vitro. The structure-activity relationship indicated that a free hydroxyl in the C-3 position contributed to the activity. Free hydroxyls at the 4, 8, and 15 positions interfered with the activity, and their estrification resulted in improved cytotoxicity. The cytotoxic activity of these trichothecenes did not seem to be related to their degree of lipophilicity. Adriamycin-resistant P388 cells were cross-resistant to the trichothecenes, and this resistance could be circumvented by verapamil.

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Adriamycin-resistant P388 cells

ED50 :

the concentration inhibiting the growth rate by 50%


octanol-water partitioning coefficient


  1. 1.

    Claridge CA, Schmitz H, Bradner WT (1979) Antitumor activity of some microbial and chemical transformation products of anguidine (4,15-diacetoxyscirpene-3-ol). Cancer Chemother Pharmacol 2:181

  2. 2.

    Douros J, Matthew S (1978) New natural products of interest under development at the National Cancer Institute. Cancer Chemother Pharmacol 1:91

  3. 3.

    Doyle TW, Bradner WT (1980) Trichothecanes. In: Cassidy JM, Douros J (eds) Anticancer agents based on natural product models. Academic, New York, p 43

  4. 4.

    Ellison RA, Kotsonis FN (1974) In vitro metabolism of T-2 toxin. Appl Microbiol 27:423

  5. 5.

    Grove JF, Mortimer P (1969) The cytotoxicity of some transformation products of diacetoxyscirpenol. Biochem Pharmacol 18:1473

  6. 6.

    Hansch C (1971) Quantitative structure-activity relationship in drug design. In: Ariens EJ (ed) Drug design, vol 1. Academic, New York, p 271

  7. 7.

    Johnson RK, Chitnis MP, Embrey WM, Gregory EB (1978) In vivo characteristics of resistance and cross-resistance of an Adriamycin-resistant subline of P388 leukemia. Cancer Treat Rep 62:1535

  8. 8.

    Kozarich JW, Stubbe J, Griffith RK, Sartorelli AC (1979) Approaches to the acquisition of new anticancer drugs: analog development. Methods Cancer Res 16:127

  9. 9.

    Ramu A, Spanier R, Rahamimoff H, Fuks Z (1984) Restoration of doxorubicin responsiveness in doxorubicin-resistant P388 murine leukemia cells. Br J Cancer 50:501

  10. 10.

    Ramu A, Fuks Z, Gatt S, Glaubiger D (1984) Reversal of acquired resistance to doxorubicin in P388 murine leukemia cells by perhexiline maleate. Cancer Res 44:144

  11. 11.

    Robb J, Norval M (1983) Comparison of cytotoxicity and thin-layer chromatography methods for detection of mycotoxins. Appl Environ Microbiol 46:948

  12. 12.

    Rottem S, Yagen B, Katznell A (1984) Effect of trichothecenes on growth and intracellular pool size of Mycoplasma gallisepticum. FEBS Lett 175:189

  13. 13.

    Suffness M, Douros J (1979) Drugs of plant origin. Methods Cancer Res 16:73

  14. 14.

    Tsuruo T, Lida H, Tsukagoshi S, Sakurai Y (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41:1967

  15. 15.

    Ueno Y (1983) General toxicology. In: Ueno Y (ed) Trichothecenes, chemical, biological and toxicological aspects. Elsevier, Amsterdam, p 135

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Ramu, A., Yagen, B. & Ramu, N. The cytotoxicity of T-2 toxin and related 12,13-epoxytrichothecenes to Adriamycin-sensitive and-resistant P388 leukemia cells. Cancer Chemother. Pharmacol. 24, 264–267 (1989). https://doi.org/10.1007/BF00257631

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  • Hydroxyl
  • Leukemia
  • Cancer Research
  • Verapamil
  • Leukemia Cell