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Comparative toxicity of fostriecin, hepsulfam and pyrazine diazohydroxide to human and murine hematopoietic progenitor cells in vitro

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Summary

The in vitro myelotoxic potentials of three investigational antitumor agents, Fostriecin, Hepsulfam and pyrazine diazohydroxide (PZDH), were evaluated utilizing clonogenic assays. Human and murine marrow cells were exposed to each drug for 1 hr prior to culture in microcapillary (human) or Petri dish (murine) assays. Fostriecin (0.22–220 μM), Hepsulfam (0.34–340 μM) and PZDH (0.68–680 μM) inhibited myeloid (CFU-gm), erythroid (BFU-e, CFU-e) and megakaryocytic (CFU-meg) colony formation in a concentration-dependent manner. CFU-e from both species were more sensitive to Fostriecin than the other progenitors and murine cells more sensitive overall to Fostriecin than their human counterparts. Murine CFU-e were also more sensitive to Hepsulfam than human CFU-e, with CFU-gm and BFU-e being similarly affected in both species. Human BFU-e were greatly inhibited by PZDH, whereas murine BFU-e were relatively resistant to its toxic effects. Fostriecin was the most toxic of the three antitumor agents, with PZDH the least toxic.

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Author notes

  1. De-Lin Du

    Present address: Institute of Basic Medical Sciences, Beijing, PRC

  2. Donna A. Volpe & Charles K. Grieshaber

    Present address: Food and Drug Administration, Rockville, MD, USA

Authors and Affiliations

  1. Hipple Cancer Research Center, 4100 South Kettering Boulevard, 45439-2092, Dayton, OH, USA

    De-Lin Du, Donna A. Volpe & Martin J. Murphy Jr.

  2. National Cancer Institute, Bethesda, MD, USA

    Charles K. Grieshaber

Authors
  1. De-Lin Du
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  2. Donna A. Volpe
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  3. Charles K. Grieshaber
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  4. Martin J. Murphy Jr.
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Du, DL., Volpe, D.A., Grieshaber, C.K. et al. Comparative toxicity of fostriecin, hepsulfam and pyrazine diazohydroxide to human and murine hematopoietic progenitor cells in vitro . Invest New Drugs 9, 149–157 (1991). https://doi.org/10.1007/BF00175082

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