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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Aug;80(16):5090–5093. doi: 10.1073/pnas.80.16.5090

Polyamine biosynthesis is required for the maintenance of peripheral blood cell elements in the rat.

G D Luk, S J Sharkis, M D Abeloff, P P McCann, A Sjoerdsma, S B Baylin
PMCID: PMC384194  PMID: 6410400

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 improvement. Thus, the maintenance of normal, adult rat hematologic parameters, as with the proliferation of neoplastic and transformed cells in culture, is critically dependent on continued polyamine biosynthesis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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