OXIDANT-INDUCED DNA DAMAGE OF TARGET-CELLS
OXIDANT-INDUCED DNA DAMAGE OF TARGET-CELLS
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DOI：
10.1172/jci113660
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发表时间：
1988-09-01
影响因子：
15.9
通讯作者：
COCHRANE, CG
中科院分区：
文献类型：
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作者：
SCHRAUFSTATTER, I;HYSLOP, PA;COCHRANE, CG
在这项研究中，我们研究了白细胞氧化剂种类，诱导氧化损伤的DNA在整个细胞。以微摩尔浓度（10-100 μ M）在细胞外加入的H2 O2诱导各种靶细胞中的DNA链断裂。特定靶细胞的敏感性与其过氧化氢酶含量和靶细胞去除H2 O2的速率呈负相关。由黄嘌呤氧化酶/嘌呤或佛波酯肉豆蔻酸酯刺激的单核细胞产生的氧化剂种类诱导靶细胞的DNA断裂与产生的H2 O2的量成比例。这些DNA链断裂被细胞外过氧化氢酶阻止，但不是由超氧化物歧化酶。细胞毒性剂量的HOCl，添加到靶细胞，不诱导DNA链断裂，髓过氧化物酶添加在细胞外的H2 O2产生系统的存在下，防止DNA链断裂的形成成比例的H2 O2降解能力。研究还表明，H2 O2在细胞内形成羟基自由基（.OH），这似乎是最有可能导致DNA损伤的自由基：在暴露于H2 O2的细胞中检测到.OH;在暴露于H2 O2的细胞中DNA碱基脱氧鸟苷被羟基化;细胞内铁对诱导DNA链断裂至关重要。
In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 .mu.M) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks.