Molecular interactions of ruthenium complexes in isolated mammalian nuclei and cytotoxicity on V79 cells in culture

Abstract

In this paper, the molecular interactions in isolated mammalian nuclei of three ruthenium complexes, which are putative antineoplastic chemotherapeutic agents effective in reducing metastatic tumours in vivo, have been investigated and compared with the well-known antitumour drug CDDP ( cis-diamminedichloroplatinum). The compounds studied are: Na trans-RuCl 4(DMSO)Imidazole (NAMI), Na trans-RuCl 4(DMSO)Oxazole (NAOX) and Na trans-RuCl 4(TMSO)Isoquinoline (TEQU). This study shows that the drugs bind to DNA but induce few, if any, DNA interstrand crosslinks, which are considered as the main biological lesions involved in the cytotoxic activity of several already known antitumour drugs, whilst in the same experimental conditions, CDDP is confirmed to induce them. On the other hand, proteins appear to be an important target in the cell for these drugs, since proteins-DNA crosslinks are shown to be induced by the complexes. Moreover, we investigated Ru complexes for their direct cytotoxicity on V79 cells in culture, showing that two of them (NAMI and NAOX) do not significantly reduce the cloning efficiency of the cells even at concentrations as high as 2–3 mg/ml: only TEQU both reduces cloning efficiency and induces a significant number of mutants in V79 cells in culture.