Binding to cellular macromolecules as a possible mechanism for the cytotoxicity of misonidazole.
Binding to cellular macromolecules as a possible mechanism for the cytotoxicity of misonidazole.
复制标题
与细胞大分子的结合是米索硝唑细胞毒性的可能机制。
作者：
A. J. Varghese;G. Whitmore
在氯化铵存在下，用锌粉在水溶液中处理[14C]咪唑时，硝基被还原。当还原混合物与小牛胸腺DNA或牛血清白蛋白反应时，放射性既与DNA结合，又与蛋白质结合。在相同条件下，咪唑不与这些大分子结合。对还原混合物的分析表明，咪唑硝唑的主要产物为羟胺、胺和偶氮类化合物。在给予[14C]咪唑硝唑后的C3H小鼠的许多组织中，在DNA、RNA和蛋白质组分中检测到放射性。中国仓鼠卵巢细胞在无氧条件下与药物孵育也得到了类似的结果。推测硝基还原和硝基还原产物与大分子的结合可能是咪唑类化合物具有致突变和细胞毒性作用的机制。
Reduction of the nitro group occurred when [14C]misonidazole was treated with zinc dust in aqueous solution in the presence of ammonium chloride. When the reduction mixture was allowed to react with calf thymus DNA or bovine albumin, radioactivity was bound to both DNA and protein. Under the same conditions, misonidazole did not bind to these macromolecules. Analysis of the reduction mixture indicated that the hydroxylamine, amine, and hydrazo derivatives of mizonidazole were the major products. In a number of tissues of C3H mice after administration of [14C]misonidazole, radioactivity was detected in the DNA, RNA, and protein fractions. Similar results were also obtained with Chinese hamster ovary cells incubated with the drug in the absence of oxygen. It is postulated that nitroreduction and binding of the nitroreduction products to macromolecules is a probable mechanism for the mutagenic and cytotoxic properties of misonidazole.