Jacobson B, Biaglow J E, Fielden E M, Adams G E
Cancer Clin Trials. 1980 Spring;3(1):47-53.
A number of nitro compounds behave as electron acceptors with ascorbate in a non-enzyme-catalyzed reaction and with NADPH as electron donor in an enzyme-catalyzed reaction with liver homogenate. In both systems, the oxygen consumption is conveniently monitored by a Clark-type oxygen electrode. The oxygen consumption by S9 homogenate was found to be influenced by the electron affinity of the nitro compound. Detailed studies with misonidazole as the electron acceptor demonstrated that the oxygen consumption was influenced by protein and drug concentrations. Various inhibitors of electron transfer reactions, such as rotenone, antimycin A, and sodium azide, had no effect on misonidazole-stimulated oxygen utilization. However, cyanide was found to be stimulating in this system and this may be due to the inhibition of enzymes such as catalase and superoxide dismutase known to be present in S9. The oxygen consumption by S9 did not appear to be due to a hydroxylating reaction because metyrapone, a known inhibitor of this reactions, had no effect. Methional, a hydroxyl radical scavenger, was inhibitory as was glutathione. Clelands reagent had no effect. Additional studies with thiol-reactive agents suggest that a protein thiol may be important for the enzyme-catalyzed reaction between NADPH, misonidazole, and oxygen.
许多硝基化合物在非酶催化反应中可作为电子受体与抗坏血酸盐反应，并在与肝匀浆的酶催化反应中以NADPH作为电子供体。在这两种体系中，氧消耗都可以通过克拉克型氧电极方便地监测。发现S9匀浆的氧消耗受硝基化合物电子亲和力的影响。以米索硝唑作为电子受体的详细研究表明，氧消耗受蛋白质和药物浓度的影响。各种电子传递反应抑制剂，如鱼藤酮、抗霉素A和叠氮化钠，对米索硝唑刺激的氧利用没有影响。然而，发现氰化物在该体系中具有刺激作用，这可能是由于抑制了已知存在于S9中的过氧化氢酶和超氧化物歧化酶等酶。S9的氧消耗似乎不是由于羟化反应，因为已知该反应的抑制剂美替拉酮没有作用。甲硫醛是一种羟基自由基清除剂，与谷胱甘肽一样具有抑制作用。克莱兰试剂没有作用。用硫醇反应剂进行的进一步研究表明，蛋白质硫醇可能对NADPH、米索硝唑和氧之间的酶催化反应很重要。
