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Toxicologic Pathology
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Journal Article

Apoptosis in the Central Nervous System of Developing Mouse Fetuses from 5-Azacytidine-Administered Dams

Mokbul Md. Hossain

Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan

Hiroyuki Nakayama

Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan

Naoaki Goto

Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan

To determine the effect of 5-azacytidine (5Az), a cytidine analogue, on the developing fetus, different strains of mice were injected with various doses of the agent, ip, at 11 days of gestation. Light microscopically, severely pyknotic cell death profiles were observed in different layers of the developing brain and spinal cord (central nervous system) on the day after the injection. Electron microscopy of the pyknotic cells revealed the shrinkage of the cell body, to various degrees margination of the nuclear chromatin, condensation of nuclear materials, fragmentation of the affected cells, and, finally, neat "bite-size" bodies engulfed by surrounding normal neuroepithelial cells and macrophage-like cells. DNA fragmentation was detected in the nuclei of the pyknotic cells by an in situ detection method for fragmented DNA ends. These changes were consistent with the criteria of apoptosis.

Key Words: 5-Azacytidine • apoptosis • central nervous system • mouse fetus • TUNEL method

Toxicologic Pathology, Vol. 23, No. 3, 367-372 (1995)
DOI: 10.1177/019262339502300313


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