Kerr J F, Winterford C M, Harmon B V
Department of Pathology, University of Queensland Medical School, Herston, Australia.
Cancer. 1994 Apr 15;73(8):2013-26. doi: 10.1002/1097-0142(19940415)73:8<2013::aid-cncr2820730802>3.0.co;2-j.
Apoptosis is a distinct mode of cell death that is responsible for deletion of cells in normal tissues; it also occurs in specific pathologic contexts. Morphologically, it involves rapid condensation and budding of the cell, with the formation of membrane-enclosed apoptotic bodies containing well-preserved organelles, which are phagocytosed and digested by nearby resident cells. There is no associated inflammation. A characteristic biochemical feature of the process is double-strand cleavage of nuclear DNA at the linker regions between nucleosomes leading to the production of oligonucleosomal fragments. In many, although not all of the circumstances in which apoptosis occurs, it is suppressed by inhibitors of messenger RNA and protein synthesis. Apoptosis occurs spontaneously in malignant tumors, often markedly retarding their growth, and it is increased in tumors responding to irradiation, cytotoxic chemotherapy, heating and hormone ablation. However, much of the current interest in the process stems from the discovery that it can be regulated by certain proto-oncogenes and the p53 tumor suppressor gene. Thus, c-myc expression has been shown to be involved in the initiation of apoptosis in some situations, and bcl-2 has emerged as a new type of proto-oncogene that inhibits apoptosis, rather than stimulating mitosis. In p53-negative tumor-derived cell lines transfected with wild-type p53, induction of the gene has, in rare cases, been found to cause extensive apoptosis, instead of growth arrest. Finally, the demonstration that antibodies against a cell-surface protein designated APO-1 or Fas can enhance apoptosis in some human lymphoid cell lines may have therapeutic implications.
细胞凋亡是一种独特的细胞死亡方式，负责正常组织中细胞的清除；它也发生在特定的病理情况下。在形态学上，它涉及细胞的快速浓缩和出芽，形成含有保存完好细胞器的膜包裹凋亡小体，这些凋亡小体被附近的驻留细胞吞噬和消化。没有相关的炎症反应。该过程的一个典型生化特征是核小体间连接区的核DNA双链断裂，导致寡核小体片段的产生。在许多（尽管不是所有）细胞凋亡发生的情况下，它会被信使RNA和蛋白质合成抑制剂所抑制。细胞凋亡在恶性肿瘤中自发发生，常常显著延缓其生长，并且在对放疗、细胞毒性化疗、加热和激素去除有反应的肿瘤中会增加。然而，目前对该过程的许多兴趣源于发现它可以被某些原癌基因和p53肿瘤抑制基因所调控。因此，已表明c-myc表达在某些情况下参与细胞凋亡的起始，并且bcl-2已成为一种新型的抑制细胞凋亡而非刺激有丝分裂的原癌基因。在用野生型p53转染的p53阴性肿瘤来源细胞系中，在罕见情况下发现该基因的诱导会导致广泛的细胞凋亡，而不是生长停滞。最后，针对一种名为APO-1或Fas的细胞表面蛋白的抗体可增强某些人淋巴细胞系中的细胞凋亡，这一发现可能具有治疗意义。
