Sulphydryls, ascorbate and oxygen as modifiers of the toxicity and metabolism of misonidazole in vitro.
Sulphydryls, ascorbate and oxygen as modifiers of the toxicity and metabolism of misonidazole in vitro.
复制标题
巯基、抗坏血酸和氧作为米索硝唑体外毒性和代谢的调节剂。
作者：
Y. Taylor;A. Rauth
等摩尔浓度的半胱胺和还原型谷胱甘肽保护5 mM米索硝唑（MISO）的细胞毒性，而5 mM抗坏血酸增强其毒性缺氧CHO和HeLa细胞在体外。当在稍后的孵育时间加入半胱胺时，也可以看到保护（肩部区域的再现）。这些毒性的变化伴随着药物代谢的变化，这一点可以通过用14C标记的MISO处理后获得的细胞提取物的放射性色谱图来证明。相比之下，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性色谱图表明没有药物代谢。在低氧暴露于MISO期间，通过引入O2可以立即停止毒性和药物代谢。这些观察结果进行了讨论的MISO的代谢介导的毒性和sulphydryls和O2可能发挥的作用的一个可能的模型。
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.