RADICAL ANION METABOLITES

这项研究的目的是确定FREE所扮演的角色 外源物质还原代谢中的自由基。厌氧症 培养几乎所有的硝基芳香族外来生物，例如硝基苯，通过 大鼠肝脏的微粒体、线粒体或胞浆部分 NADH或NADPH的存在会导致多线电子自旋 硝基阴离子自由基的共振光谱特征。我们有 现在证明了硝基阴离子自由基的形成是通过线粒体 内源性辅因子。硝基药物不会影响线粒体的呼吸， 尤其是与ADP的耦合。硝基还原的位置，如 由线粒体传输链的抑制物决定，似乎是 NADH脱氢酶和外膜NAD(P)H细胞色素C还原酶。 卤素取代的硝基化合物是辐射增敏剂，是 最有毒的硝基化合物。硝基芳香族阴离子对卤化物的损失 形成一种非常活泼的以碳为中心的自由基，通过自旋检测到 陷阱，它与细胞大分子发生反应。不可逆转的 这些硝基化合物与DNA、蛋白质等的结合可被抑制 自旋陷阱。 大鼠肝微粒体细胞色素P-450还原形成自由基 还研究了龙胆紫、SO2、CCl4和O2。

The objective of this study is to determine the role played by free radicals in the reductive metabolism of xenobiotics. The anaerobic incubation of almost all nitroaromatic xenobiotics, e.g., nitrobenzene, by the microsomal, mitochondrial, or cytosolic fractions of rat liver in the presence of either NADH or NADPH, leads to a multiple-line electron spin resonance spectrum characteristic of the nitro anion free radical. We have now demonstrated nitro anion radical formation by mitochondria using endogenous cofactors. Nitro drugs do not affect mitochondrial respiration, in particular the coupling to ADP. The sites of nitro reduction, as determined by inhibitors of the mitochondrial transport chain, appear to be NADH dehydrogenase and outer-membrane NAD(P)H cytochrome c reductase. Halogen-substituted nitro compounds are radiosensitizers and are among the most toxic nitro compounds. Loss of halide by the nitroaromatic anion forms a very reactive carbon-centered free radical, detected by spin trapping, which reacts with cellular macromolecules. The irreversible binding of these nitro compounds to DNA, protein, etc. may be inhibited by spin traps. Free radical formation by hepatic microsomal cytochrome P-450 reduction of gentian violet, SO2, CCl4 and O2 has also been investigated.