The nature of cytotoxic drug-induced cell death in murine intestinal crypts.
The nature of cytotoxic drug-induced cell death in murine intestinal crypts.
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DOI：
10.1038/bjc.1992.113
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发表时间：
1992-04
影响因子：
8.8
通讯作者：
Alison, M R
中科院分区：
文献类型：
--
作者：
Anilkumar, T V;Sarraf, C E;Hunt, T;Alison, M R
本文研究了四种潜在致死剂量的肿瘤化疗药物引起的小鼠小肠隐窝细胞死亡的性质。所用药物为阿糖胞苷、长春新碱、阿霉素和氮芥。化合物容易诱导大量细胞死亡的隐窝的增殖区室。在每种情况下，细胞死亡在1小时内明显，并且死细胞的发生率在随后的4-8小时内达到峰值。到24小时，在地穴系统中几乎没有损伤。值得注意的是，死细胞或死细胞碎片被邻近的健康肠上皮细胞迅速吞噬（约1小时内）。当通过光学显微镜、透射电子显微镜和扫描电子显微镜检查时，死细胞显示出已经屈服于细胞死亡的凋亡模式的特征，而没有任何坏死特征的细胞和细胞器水肿的痕迹。该研究表明，即使细胞受到严重的病理扰动，细胞凋亡引起的细胞死亡也会起作用，而且这种现象不仅仅是一个对生理刺激或轻微的物理或化学创伤作出反应的过程。
The nature of cell death in murine small intestinal crypts caused by potentially lethal doses of four classes of cancer chemotherapeutic agents was studied. The drugs used were cytosine arabinoside, vincristine, adriamycin and nitrogen mustard. The compounds readily induced massive cell death in the proliferating compartment of the crypt. In each case, cell death was apparent within an hour, and the incidence of dead cells peaked during the following 4-8 h. By 24 h, little damage was discernible in the crypt systems. Remarkably, dead cells or dead cell fragments were phagocytosed rapidly (within about 1 h) by neighbouring healthy enterocytes. When examined by light microscopy, transmission electron microscopy and scanning electron microscopy, the dead cells showed the characteristic features of having succumbed to an apoptotic mode of cell death without any trace of cell and organelle oedema characteristic of necrosis. The study suggests that cell death by apoptosis operates even when the cells are exposed to severe pathological perturbation and that the phenomenon is not solely a process which operates in response to either physiological stimuli or to mild physical or chemical trauma.