Raffray M, Cohen G M
MRC Toxicology Unit, University of Leicester, UK.
Pharmacol Ther. 1997 Sep;75(3):153-77. doi: 10.1016/s0163-7258(97)00037-5.
Mounting evidence indicates that apoptosis rather than necrosis predominates in many cytolethal toxic injuries. Associated cell death models of apoptosis and necrosis are either: (1) totally separate death modes, (2) a continuum whereby they are extremes of biochemically overlapping death pathways, or (3) essentially distinct processes with only limited molecular and cell biology overlap. We conclude that the current balance of evidence favours the third of these options. The established axiom that, even when considering the same toxicant, injury amplitude (dose) is a primary determinant of whether cells die via active cell death (apoptosis) or failure of homeostasis (necrosis) remains valid. Tissue selectivity of toxicants can stem from the apoptotic or necrotic thresholds at which different cells die, as well as targeting factors such as toxicokinetics, receptor recognition, bioactivation, and cell-specific lesions.
越来越多的证据表明，在许多细胞致死性毒性损伤中，凋亡而非坏死占主导。凋亡和坏死相关的细胞死亡模型有以下几种情况：（1）完全独立的死亡模式；（2）一个连续统一体，即它们是生物化学上重叠的死亡途径的极端情况；或者（3）本质上不同的过程，只有有限的分子和细胞生物学重叠。我们得出结论，目前的证据平衡支持这些选项中的第三种。既定的公理是，即使考虑相同的毒物，损伤幅度（剂量）也是细胞通过主动细胞死亡（凋亡）还是内稳态失败（坏死）死亡的主要决定因素，这一公理仍然有效。毒物的组织选择性可能源于不同细胞死亡的凋亡或坏死阈值，以及诸如毒物动力学、受体识别、生物活化和细胞特异性损伤等靶向因素。
