Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct-[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine], by in vitro and in vivo assays.

Abstract

Considering the promising previous results of ct-[RuCl(CO)(dppb)(bipy)]PF6 (where dppb=1,4-bis(diphenylphosphino)butane and bipy=2,2'-bipyridine) as an antitumor agent, novel biological assays evaluating its toxicogenic potential were performed. The genotoxicity of the compound was evaluated by the in vitro micronucleus test (V79, Chinese hamster lung fibroblasts; HepG2, hepatocellular carcinoma cells), in vivo bone marrow micronucleus test and comet assay in hepatocytes (Swiss mice). The animals were treated with 0.63, 1.25, 2.5 and 5.0mg/kg body weight (bw) of the compound. Negative (water) and positive (cisplatin, 1.5mg/kg bw; methyl methanesulfonate, 40mg/kg bw) controls were included. The parameters considered in the comet assay were the percentage of tail DNA, tail moment and tail length. The results of the in vitro micronucleus tests showed the absence of genotoxicity in V79 cells, while the compound was genotoxic in HepG2 cells at a concentration of 1.25μm. In the in vivo micronucleus test, the compound was not genotoxic at the different doses evaluated. In the comet assay, only the dose of 5.0mg/kg bw resulted in a significant increase in the frequency of DNA damage in hepatocytes when compared to the negative control. The genotoxic effect observed in HepG2 cells and in the liver comet assay indicates that the compound was metabolized by hepatic cells.