Chromosome-damaging activity of a ruthenium radiosensitizer, RuCl2 (DMSO)2 (4-nitroimidazole)2, in Chinese hamster ovary cells in vitro

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.