毒理学相关资料,第五章内容参考文献29.docVIP

Mechanisms of Cell Injury by Activated Oxygen Species John L. FarberDepartment of Pathology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania Abstract 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. -- Environ Health Perspect 102(Suppl 10):17-24 (1994) Key words: superoxide, hydrogen peroxide, hydroxyl radical, iron, lipid peroxidation, mitochondria, DNA, poly(ADP-ribose)polymerase Environmental Health Perspectives 102, Supplement 10, December 1994 Mechanisms of Cell Injury by Activated Oxygen Species John L. Farber Department of Pathology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania AbstractCurrent 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-