Anilkumar T V, Sarraf C E, Hunt T, Alison M R
Department of Histopathology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Br J Cancer. 1992 Apr;65(4):552-8. doi: 10.1038/bjc.1992.113.
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.
研究了四类癌症化疗药物的潜在致死剂量对小鼠小肠隐窝细胞死亡性质的影响。所用药物为阿糖胞苷、长春新碱、阿霉素和氮芥。这些化合物很容易在隐窝的增殖区诱导大量细胞死亡。在每种情况下，细胞死亡在一小时内就很明显，死细胞的发生率在接下来的4-8小时内达到峰值。到24小时时，隐窝系统几乎没有可见损伤。值得注意的是，死细胞或死细胞碎片被相邻的健康肠上皮细胞迅速吞噬（约1小时内）。通过光学显微镜、透射电子显微镜和扫描电子显微镜检查发现，死细胞呈现出凋亡性细胞死亡的特征，没有任何坏死特有的细胞和细胞器水肿痕迹。该研究表明，即使细胞受到严重的病理扰动，凋亡性细胞死亡仍会发生，而且这种现象不仅仅是一个响应生理刺激或轻度物理或化学创伤而发生的过程。
