Comparative toxicity of fostriecin, hepsulfam and pyrazine diazohydroxide to human and murine hematopoietic progenitor cells in vitro.
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 microM), Hepsulfam (0.34-340 microM) and PZDH (0.68-680 microM) 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.
Du
D L
DL
Hipple Cancer Research Center, Dayton, OH.
Volpe
D A
DA
Grieshaber
C K
CK
Murphy
M J
MJ
D000475:Alkenes / Q000633:toxicity; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay / Q000379:methods; D015507:Drugs, Investigational / Q000633:toxicity; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D011090:Polyenes; D011719:Pyrazines / Q000633:toxicity; D011753:Pyrones; D013451:Sulfonic Acids / Q000633:toxicity
D000475:Alkenes; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D011090:Polyenes; D011719:Pyrazines; D011753:Pyrones; D013451:Sulfonic Acids; C051397:pyrazine-2-diazohydroxide; C052475:hepsulfam; C040313:fostriecin