Farber J L
Department of Pathology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Environ Health Perspect. 1994 Dec;102 Suppl 10(Suppl 10):17-24. doi: 10.1289/ehp.94102s1017.
Current evidence suggests that O2- and H2O2 injure cells as a result of the generation of a more potent oxidizing species. In addition to O2- and H2O2, the third essential component of the complex that mediates the lethal cell injury is a cellular source of ferric iron. The hypothesis most consistent with all the available data suggests that O2- reduces a cellular source of ferric to ferrous iron, and the latter then reacts with H2O2 to produce a more potent oxidizing species, like the .OH or an equivalently reactive species. In turn, .OH initiates the peroxidative decomposition of the phospholipids of cellular membranes. .OH also damages the inner mitochondrial membrane. Upon mitochondrial deenergization, a sequence of events is initiated that similarly leads to the loss of viability of the cell. DNA represents a third cellular target of .OH. Depending on the cell type, oxidative DNA damage can be coupled to cell killing through a mechanism related to the activation of poly (ADP-ribose) polymerase.
目前的证据表明，超氧阴离子（O2-）和过氧化氢（H2O2）会因产生更强效的氧化物种而损伤细胞。除了O2-和H2O2外，介导致死性细胞损伤的复合物的第三个关键成分是三价铁的细胞来源。与所有现有数据最为一致的假说表明，O2-将细胞内的三价铁还原为二价铁，然后二价铁与H2O2反应生成更强效的氧化物种，如羟基自由基（·OH）或同等活性的物种。反过来，·OH引发细胞膜磷脂的过氧化分解。·OH还会损伤线粒体内膜。线粒体去极化后，一系列事件开始发生，同样会导致细胞活力丧失。DNA是·OH的第三个细胞靶点。根据细胞类型的不同，氧化性DNA损伤可通过与聚（ADP-核糖）聚合酶激活相关的机制与细胞死亡相联系。
