Chan P K, Skov K A, James B R, Farrell N P
Chem Biol Interact. 1986 Oct 1;59(3):247-54. doi: 10.1016/s0009-2797(86)80070-9.
The metal complex, RuCl2 (DMSO)2 (4-nitroimidazole)2, 1, which has hypoxic radiosensitizing properties, was examined for genotoxic activity, as measured by the in vitro induction of chromosome aberrations (chromatid breaks and chromatid exchanges) in Chinese hamster ovary (CHO) cells. A dose-dependent increase in the frequencies of metaphases with chromatid aberrations was observed for 1. Addition of S9 liver microsomal mixture and 1 to the cultured CHO cells did not alter the clastogenic activity noted for the complex itself. The clastogenic (chromosome damaging) activity of a precursor complex, cis-RuCl2(DMSO)4 and the ligand, 4-nitroimidazole (4-NO2-Im) were found to be less than that of 1 at corresponding concentrations. A comparison with two drugs used clinically with radiation, cis-dichlorodiammineplatinum(II) (cis-DDP) and misonidazole (miso), indicated that the clastogenic activity of 1 was similar to miso and much less than that of cis-DDP.
具有低氧放射增敏特性的金属配合物RuCl2 (DMSO)2 (4-硝基咪唑)2（1），通过体外诱导中国仓鼠卵巢（CHO）细胞染色体畸变（染色单体断裂和染色单体交换）来检测其遗传毒性活性。对于1，观察到具有染色单体畸变的中期细胞频率呈剂量依赖性增加。向培养的CHO细胞中添加S9肝微粒体混合物和1并没有改变该配合物本身所观察到的致断裂活性。发现前体配合物顺式-RuCl2(DMSO)4和配体4-硝基咪唑（4-NO2-Im）在相应浓度下的致断裂（染色体损伤）活性低于1。与临床上与放疗联合使用的两种药物顺式二氯二氨铂（II）（顺铂）和米索硝唑（米索）进行比较表明，1的致断裂活性与米索相似，远低于顺铂。
