The effect of macrophage development on the release of reactive oxygen intermediates and lipid oxidation products, and their ability to induce oxidative DNA damage in mammalian cells.
The effect of macrophage development on the release of reactive oxygen intermediates and lipid oxidation products, and their ability to induce oxidative DNA damage in mammalian cells.
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巨噬细胞发育对活性氧中间体和脂质氧化产物释放的影响，以及它们在哺乳动物细胞中诱导氧化性 DNA 损伤的能力。
DOI：
10.1093/carcin/7.5.813
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发表时间：
1986
期刊：
影响因子：
4.7
通讯作者：
Adams,DO
中科院分区：
文献类型：
--
作者：
Lewis,JG;Hamilton,T;Adams,DO
炎症和潜在有害物质的释放，如来自炎症细胞的活性氧中间体（ROI）和脂质氧化产物，与癌变的增强有关。在共培养的哺乳动物细胞中，小鼠巨噬细胞受到磷酸酯刺激时，可诱导5,6环饱和胸腺嘧啶残基（T'），这是一种已知氧化起源的损伤。过氧化氢酶可以抑制这种损伤的诱导，而过氧化氢试剂可以在靶细胞中诱导这种损伤。在本研究中，我们使用具有高、低和中等释放h2o2或花生四烯酸（AA）代谢物能力的巨噬细胞群体来评估这类化合物对诱导饱和胸腺嘧啶的相对贡献。被卡介苗（Bacillus Calmette-Guerin， BCG）激活的巨噬细胞对h2o2的释放能力最高，对AA代谢物的释放能力最低，它们诱导的饱和胸腺嘧啶水平最低。来自未处理腹膜的常驻巨噬细胞产生h2o2的能力最低，释放AA代谢物的能力最高，比BCG巨噬细胞诱导更多的饱和胸腺嘧啶。酪蛋白诱导的炎性巨噬细胞具有释放h2o2和AA代谢物的中等能力，可诱导最高水平的饱和胸腺嘧啶。Zymosan诱导AA代谢物的释放量大于H2O2的释放量，对T′的诱导效果优于TPA，而TPA对H2O2的分泌效果优于TPA。北二氢愈创木酸（NDGA）是AA代谢的氧合酶和环合酶途径的抑制剂，对T′的诱导有抑制作用。由常驻巨噬细胞。吲哚美辛是环加氧酶途径的抑制剂，可增强T′的诱导。综上所述，这些数据表明，虽然h2o2在3T3细胞中具有诱导T'的能力，但它可能不是DNA损伤的唯一介质，脂氧合酶产生的AA代谢物可能（单独或与ROI协同）在巨噬细胞诱导DNA氧化损伤中发挥重要作用。
Inflammation and the release of potentially damaging substances, such as reactive oxygen intermediates (ROI) and lipid oxidation products from inflammatory cells, have been linked to the potentiation of carcinogenesis. Murine macrophages when stimulated with phorbol esters induce 5, 6 ring saturated thymine residues (T'), a lesion of known oxidative origin, in co-cultivated mammalian cells. Induction of this damage was inhibited by catalase and induced in target cells by reagent H2O2alone. In the present studies, we used defined populations of macrophages with high, low and intermediate capacities for the release of H2O2or metabolites of arachidonic acid (AA) to assess the relative contribution of these classes of compounds to the induction of saturated thymines. Macrophages activated with Bacillus Calmette-Guerin (BCG), which have the highest capacity for the release of H2O2and the lowest for the release of metabolites of AA, induced the lowest levels of saturated thymines. Resident macrophages from the unmanipulated peritoneum, which have the lowest capacity for the production of H2O2and the highest capacity for release of AA metabolites, induced more saturated thymines than did the BCG macrophages. Inflammatory macrophages elicited by casein, which have an intermediate capacity for release of H2O2and AA metabolites, induced the highest level of saturated thymines. Zymosan, which induced more release of AA metabolites than release of H2O2, was a better stimulant for the induction of T' than TPA, which is a better stimulant for secretion of H2O2. Nordihydroguaiaretic acid (NDGA), an inhibitor of the tipoxygenase and cyclooxygenase pathways for metabolism of AA, inhibited the induction of T'. by resident macrophages. Indomethacin, an inhibitor of the cyclo-oxygenase path, enhanced induction of T'. Taken together, the data suggest that while H2O2has the capacity to induce T' in 3T3 cells, it may not be the only mediator of DNA damage and that lipoxygenase generated metabolites of AA may (alone or in concert with ROI) play an important role in the induction of oxidative DNA damage by macrophages.