Chao C F, Ting L, Subjeck J R, Johnson R J
Int J Radiat Oncol Biol Phys. 1984 Aug;10(8):1391-4. doi: 10.1016/0360-3016(84)90355-9.
The neurotoxic effect of the nitroimidazole radiosensitizers misonidazole (MISO) and desmethylmisonidazole (DMM) has seriously compromised their clinical effectiveness. We compare here the effect of MISO and DMM on oxygen consumption in purified beef heart mitochondria. MISO has been found to significantly increase the oxygen consumption rate and decrease the respiratory control ratio in isolated mitochondria when incubated in the presence of the NAD+ dependent substrate, beta-hydroxybutyrate. DMM has a similar but less pronounced effect than MISO on these respiratory parameters. When mitochondria were incubated in the presence of these radiosensitizers for 8, 15, 30, 45, and 60 minutes, the oxygen consumption rate was decreased when succinate, a FAD dependent substrate, was added following the incubation. This decrease, which is both time and dosage dependent, is equivalent for MISO and DMM.
硝基咪唑类放射增敏剂米索硝唑(MISO)和去甲基米索硝唑(DMM)的神经毒性作用严重影响了它们的临床疗效。我们在此比较了MISO和DMM对纯化的牛心线粒体耗氧量的影响。已发现,当在NAD⁺依赖性底物β-羟基丁酸存在下孵育时,MISO可显著提高分离线粒体中的耗氧率并降低呼吸控制率。DMM对这些呼吸参数的影响与MISO相似,但程度较轻。当线粒体在这些放射增敏剂存在下孵育8、15、30、45和60分钟后,加入FAD依赖性底物琥珀酸后,耗氧率降低。这种降低具有时间和剂量依赖性,MISO和DMM的情况相同。