Preclinical evaluation of hematopoietic toxicity of antileukemic agent, 5-aza-2'-deoxycytidine.
The hematopoietic toxicity of 5-aza-2'-deoxycytidine (5-AZA-CdR), an experimental antileukemic agent, was investigated in mice and dogs. Mice were administered a 12 h intravenous infusion of 5-AZA-CdR at a total dose of 20 mg/kg and at different times after treatment samples of bone marrow were analyzed for cell count, DNA synthesis and colony-forming activity (CFUc). The 5-AZA-CdR treatment produced a marked decrease in femur cell count and CFUc activity with recovery occurring on days 8-14. DNA synthesis activity increased significantly during the recovery period. Dogs were also administered a 12 h intravenous infusion at doses 3-7 mg/kg and the blood hemogram evaluated. This treatment produced a pronounced leukopenia, granulocytopenia and thrombocytopenia with a nadir between days 7-16 with recovery occurring on days 19-21. These results indicate that 5-AZA-CdR produces marked hematopoietic toxicity in mice and dogs and this toxicity appears to be reversible under these experimental conditions.
Momparler
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Département de Pharmacologie, Université de Montréal, Québec, Canada.
Gonzales
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FA
Momparler
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LF
Ma
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002452:Cell Count; D003114:Colony-Forming Units Assay; D004247:DNA / Q000096:biosynthesis; D000077209:Decitabine; D004285:Dogs; D006098:Granulocytes; D006410:Hematopoiesis / Q000187:drug effects*; D007262:Infusions, Intravenous; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D010976:Platelet Count
D000970:Antineoplastic Agents; D000077209:Decitabine; D004247:DNA; D001374:Azacitidine