Taylor Y C, Rauth A M
Br J Cancer. 1980 Jun;41(6):892-900. doi: 10.1038/bjc.1980.166.
Equimolar concentrations of cysteamine and reduced glutathione protected against the cytotoxicity of 5 mM misonidazole (MISO), whereas 5mM ascorbate enhanced its toxicity to hypoxic CHO and HeLa cells in vitro. Protection (reappearance of a shoulder region) could also be seen when cysteamine was added at later incubation times. These changes in toxicity were accompanied by changes in drug metabolism, as evidenced by radiochromatograms of cell extracts obtained after treatment with 14C-labelled MISO. In contrast, radiochromatograms obtained from cells treated with toxic levels of MISO (75 mM) under aerobic conditions indicated no drug metabolism. Both toxicity and drug metabolism could be immediately halted by introducing O2 during hypoxic exposure to MISO. These observations are discussed in terms of a possible model for the metabolism-mediated toxicity of MISO and the roles which sulphydryls and O2 may play.
等摩尔浓度的半胱胺和还原型谷胱甘肽可保护细胞免受5 mM米索硝唑（MISO）的细胞毒性，而5 mM抗坏血酸在体外增强了其对缺氧的中国仓鼠卵巢（CHO）细胞和人宫颈癌（HeLa）细胞的毒性。当在孵育后期添加半胱胺时，也可观察到保护作用（出现肩区）。这些毒性变化伴随着药物代谢的改变，用14C标记的MISO处理后获得的细胞提取物的放射色谱图证明了这一点。相反，在有氧条件下用毒性水平的MISO（75 mM）处理的细胞获得的放射色谱图表明没有药物代谢。在缺氧暴露于MISO期间引入氧气可立即停止毒性和药物代谢。根据MISO代谢介导的毒性的可能模型以及巯基和氧气可能发挥的作用对这些观察结果进行了讨论。
