Resumo

Transition metal-based compounds have been proposed as potential antitumor activity and antimestastatic behavior, in particular complexes based on ruthenium. Different studies show that these compounds presents lower systemic toxicity than the major metallodugs available to cancer treatment. Preliminary studies reported high cytotoxicity of ruthenium compounds: [Ru(N-S)(bipy)(dppb)]PF6, where bipy = 2,2’-bipyridine and dppb = 1,4-bis(difenfenilfosfina) butane and N-S = pySH (2-mercaptopiridina) and HSpym (2-mercaptopirimidina), against cancer breast cancer and lower citotoxicity on non-tumoral cells. Therefore, in order to characterize the biological activity of these two compounds, the aim of this study is to determine the mutagenic activity by Ames test, with and without metabolic activation. The Ames Salmonella/microsome mutagenicity assay is a bacterial reverse mutation assay designed to detect chemical substances that can produce genetic damage that leads to gene mutations. The test employs several histidine dependent Salmonella strains each carrying different mutations in various genes in the histidine operon. These mutations act as hot spots for mutagens that cause DNA damage via different mechanisms. When the Salmonella tester strains are grown on a minimal media agar plate, only those bacteria that revert to histidine independence are able to form colonies. The mutagens, when is added to the plate, increase the number of revertant colonies per plate, usually in a dose-related manner. The Salmonella mutagenicity assay was performed with Salmonella typhimurium strains TA97a, TA98, TA100 and TA102, with and without metabolic activation (S9 mix). The compounds was diluted in dimethylsulfoxide and tested at concentrations from 6.25 to 100 μg/plate. The plates were incubated at 37 °C for 48 h and the histidine revertant colonies were counted manually. The results show that the compounds present no mutagenic activity with or without metabolizing, by this method. It suggests that these compounds present toxicity to cancer cells without inducing mutations in healthy cells. Further studies about action mechanisms of these ruthenium compounds must be conducted to evaluate their possible use of compound on anticancer therapy. Financial support: FAPESP Processo n°: 2012/21529/7