Hossain M M, Nakayama H, Goto N
Department of Veterinary Pathology, Faculty of Agriculture, University of Tokyo, Japan.
Toxicol Pathol. 1995 May-Jun;23(3):367-72. doi: 10.1177/019262339502300313.
To determine the effect of 5-azacytidine (5 Az), 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.
为确定胞苷类似物5-氮杂胞苷（5-Az）对发育中胎儿的影响，在妊娠第11天经腹腔向不同品系的小鼠注射不同剂量的该药物。光学显微镜下，注射后第二天在发育中的脑和脊髓（中枢神经系统）的不同层观察到严重的固缩性细胞死亡形态。对固缩细胞进行电子显微镜检查发现，细胞体缩小，核染色质不同程度边缘化，核物质凝聚，受影响细胞碎片化，最后，出现被周围正常神经上皮细胞和巨噬细胞样细胞吞噬的整齐“小块”体。通过DNA片段末端原位检测方法在固缩细胞的细胞核中检测到DNA片段化。这些变化符合细胞凋亡的标准。
