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Toxicologic Pathology
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Journal Article

Hypersegmented Megakaryocytes and Megakaryocytes with Multiple Separate Nuclei in Dogs Treated with PNU-100592, an Oxazolidinone Antibiotic

John E. Lund

Worldwide Toxicology, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49001

Patricia K. Brown

Worldwide Toxicology, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49001

Megakaryocytes in normal dogs have a variety of nuclear forms. The most common variations are a single large multilobed nucleus or a segmented nucleus consisting of irregular nuclear lobes joined by strands of chromatin. Exaggerated segmentation (hypersegmentation) of the nucleus occurs in a small number of megakaryocytes. Megakaryocytes with multiple separate nuclei are infrequently observed. In a 1-mo toxicology study in young adult beagle dogs with PNU-100592, a new oxazolidinone antibacterial agent, a large increase in the number of megakaryocytes with hypersegmented nuclei and multiple separate nuclei was observed. The group mean platelet count was slightly decreased for most PNU-100592-treated groups. Siderocytes were observed on peripheral blood smears, and ring sideroblasts were present on bone marrow smears. Minimal to mild toxicologic lesions were observed in the large intestine, rectum, kidneys, liver, and testes, primarily in the high-dose group. PNU-100592 may be useful in the study of the regulation of endomitosis during megakaryocytopoiesis in the dog.

Key Words: Bone marrow • endomitosis • mucosal atrophy • sideroblasts • siderocytes • toxicology

Toxicologic Pathology, Vol. 25, No. 4, 339-343 (1997)
DOI: 10.1177/019262339702500401
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