FREE RADICAL METABOLITIES OF TOXIC CHEMICALS

这项研究的目的是确定FREE所扮演的角色 异物的还原和氧化代谢中的自由基。这个 几乎所有硝基芳香族外来生物的厌氧培养，例如， 硝基苯，由微体、线粒体或胞质组分组成 大鼠肝脏中存在NADH或NADPH，导致多线 硝基阴离子的电子自旋共振波谱特征 自由基。卤素取代的硝基化合物是辐射增敏剂和 是毒性最强的硝基化合物之一。卤化物的损失 硝基芳香族阴离子形成一种非常活泼的以碳为中心的自由基， 通过与细胞大分子发生反应的自旋捕获检测到。这个 这些硝基化合物与DNA、蛋白质等的不可逆结合可能是 被自旋陷阱抑制。肝微体形成自由基的实验研究 细胞色素P-450对龙胆紫、SO2、CC14和O2的还原作用 被调查过了。前列腺素氢过氧化物酶及其活性的研究 一个模型酶系统，辣根过氧化物酶，已经证明了 通过氧化，酶促形成自由基代谢物。ESR，在 毫秒时间尺度，揭示了一个瞬间的苯氧基的形成 对乙酰氨基酚与辣根过氧化物酶/过氧化氢反应中的自由基 和牛乳过氧化物酶/过氧化氢。短暂的激进分子显然是 与持久的顺磁性黑色素聚合物不同， 在对乙酰氨基酚存在下长时间孵育产生 氧化酶。在以下情况下检测到以硫为中心的自由基 半胱氨酸与辣根过氧化物酶和过氧化氢孵育。减少 谷胱甘肽(GSH)也被氧化成以硫为中心的自由基(GS)。通过 辣根过氧化物酶和过氧化氢。由于半胱氨酸和谷胱甘肽起着 含硫羟基在结构和功能中的重要作用 蛋白质，这些氧化反应可能调节生物功能 这些化合物。

The objective of this study is to determine the role played by free radicals in the reductive and oxidative 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 (ESR) spectrum characteristic of the nitro anion free radical. 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, CC14 and O2 has also been investigated. Investigations of the prostaglandin hydroperoxidase and a model enzyme system, horseradish peroxidase, have demonstrated the enzymatic formation of free radical metabolites by oxidation. ESR, on a millisecond time scale, has revealed the formation of a transient phenoxyl radical in the reaction of acetaminophen with horseradish peroxidase/H2O2 and bovine lactoperoxidase/H2O2. The short-lived radical is clearly distinguished from the persistent paramagnetic melanin polymers that are generated by prolonged incubation of acetaminophen in the presence of oxidizing enzymes. Sulfur-centered free radicals have been detected when cysteine was incubated with horseradish peroxidase and H2O2. Reduced glutathione (GSH) was also oxidized to a sulfur-centered radical (GS.) by horseradish peroxidase and H2O2. Since cysteine and glutathione play an important role in the structure and function of sulfhydryl-containing proteins, these oxidation reactions may modulate the biological function of these compounds.