Greenstock C L, Biaglow J E, Durand R E
Br J Cancer Suppl. 1978 Jun;3:11-5.
The metabolic activity of nitroheterocyclic sensitizers could limit their usefulness in vivo. Biochemical mechanisms of drug metabolism, toxicity and effects on cell respiration have been studied in microsomes, and the kinetics of the simulated redox reactions determined by pulse radiolysis. Stimulated oxidation of coenzyme, glucose, ascorbate or glutathione substrate radicals by nitroheterocyclic sensitizers, with the concomitant appearance of the respective nitro radical anions, is observed. Under hypoxia, the nitro radical anions decay slowly by second order processes, forming reduced metabolites. In air, the nitro radical anions react with oxygen forming superoxide radical anions, peroxide and regenerating the drug. Nitro radical-anions also react with cytochrome-c indicating a possible interference with mitochondrial energy metabolism.
硝基杂环敏化剂的代谢活性可能会限制其在体内的应用。已经在微粒体中研究了药物代谢、毒性以及对细胞呼吸影响的生化机制，并通过脉冲辐解确定了模拟氧化还原反应的动力学。观察到硝基杂环敏化剂对辅酶、葡萄糖、抗坏血酸或谷胱甘肽底物自由基的刺激氧化作用，同时出现相应的硝基自由基阴离子。在缺氧条件下，硝基自由基阴离子通过二级过程缓慢衰变，形成还原代谢物。在空气中，硝基自由基阴离子与氧气反应形成超氧自由基阴离子、过氧化物并使药物再生。硝基自由基阴离子还与细胞色素c反应，表明可能干扰线粒体能量代谢。
