Sun X M, Carthew P, Dinsdale D, Snowden R T, Cohen G M
Medical Research Council Toxicology Unit, University of Leicester, United Kingdom.
Toxicol Appl Pharmacol. 1994 Sep;128(1):78-85. doi: 10.1006/taap.1994.1182.
A time- and dose-dependent thymic atrophy was observed in young male Fischer 344 rats dosed intraperitoneally with etoposide (10, 30, or 100 mg/kg). Histopathological examination of the thymus revealed that the pattern of cell death in the majority of thymocytes had a characteristic apoptotic morphology typified by nuclear condensation. This observation was supported by the formation of internucleosomal fragments of DNA in thymocytes isolated from animals dosed with etoposide. Administration of the protein synthesis inhibitor, cycloheximide (1.5 mg/kg, ip), 1 hr prior to etoposide inhibited the induction of apoptosis in thymocytes, assessed by both biochemical and histological criteria. Flow cytometric analysis of thymocytes from animals dosed with etoposide in vivo revealed the formation of both apoptotic cells and apoptotic bodies in contrast to previous in vitro studies which showed the formation of only apoptotic cells. Our data indicate that the induction of apoptosis in thymocytes is a major mechanism involved in etoposide-induced thymic atrophy.
给年轻雄性Fischer 344大鼠腹腔注射依托泊苷（10、30或100 mg/kg）后，观察到了时间和剂量依赖性的胸腺萎缩。胸腺的组织病理学检查显示，大多数胸腺细胞的细胞死亡模式具有以核浓缩为典型特征的凋亡形态。从注射依托泊苷的动物分离的胸腺细胞中DNA核小体间片段的形成支持了这一观察结果。在依托泊苷给药前1小时腹腔注射蛋白质合成抑制剂环己酰亚胺（1.5 mg/kg），通过生化和组织学标准评估，可抑制胸腺细胞凋亡的诱导。体内注射依托泊苷的动物胸腺细胞的流式细胞术分析显示，与之前仅显示凋亡细胞形成的体外研究相反，出现了凋亡细胞和凋亡小体的形成。我们的数据表明，胸腺细胞凋亡的诱导是依托泊苷诱导胸腺萎缩的主要机制。
