Misonidazole enhances cyclophosphamide toxicity to bone marrow.
Normal bone marrow function was surveyed in animals that received cyclophosphamide after treatment with small, multiple doses of misonidazole. Peripheral blood white cell counts, cell differentials, hematocrits, bone marrow white cell counts and committed granulocyte-macrophage precursors (CFUc) were monitored for several days following treatment with misonidazole and cyclophosphamide. When results obtained from animals treated with physiological saline or misonidazole in advance of cyclophosphamide were compared, no significant differences were noted in routine assays of white blood cell count, cell morphology or hematocrit. Pre-treatment with misonidazole, however, caused a significant reduction in survival and delay in recovery of bone marrow CFUc (p less than .01). The combined use of misonidazole and cyclophosphamide also reduced animal survival (DMF = 1.2), with the majority of deaths being attributable to failure of normal hematopoietic function. These results suggest that misonidazole enhances the myelotoxicity associated with cyclophosphamide use. This additional damage is not detectable using routine hematological assays, but is demonstrable in assays of bone marrow stem cells and animal survival studies.
D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003520:Cyclophosphamide / Q000633:toxicity*; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008920:Misonidazole / Q000633:toxicity*; D009593:Nitroimidazoles / Q000633:toxicity*; D013997:Time Factors
D009593:Nitroimidazoles; D008920:Misonidazole; D003520:Cyclophosphamide