Abstract
The specific ornithine decarboxylase inhibitor alpha-difluoromethylornithine, when given to adult rats in vivo for 5 wk, resulted in a decrease in peripheral blood cell elements in normal rats and a marked suppression of marrow recovery in rats with chemotherapy-induced marrow hypoplasia. In normal rats, alpha-difluoromethylornithine resulted in a reduction of the leukocyte count to 73% of control, erythrocyte count to 61% of control, and platelet count to 24% of control. The bleeding time was increased to twice normal and 67% of the animals had epistaxis and 42% had melena. In rats treated with the S phase-specific chemotherapeutic agent 1-beta-D-arabinofuranosylcytosine, the simultaneous administration of alpha-difluoromethylornithine prevented the recovery of the bone marrow. The peripheral blood cell counts remained low--leukocyte count was 10% of control, and erythrocyte and platelet counts were 6% of control. All the animals developed epistaxis and melena and there was a 72% mortality. The administration of putrescine (4 mmol/kg, intraperitoneally, daily), the specific polyamine product of ornithine decarboxylase, reversed these hematologic effects in both normal and recovering marrow and resulted in rapid clinical improv...Continue Reading
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