Mutagenic and Genotoxic Effects of cis-(Dichloro)tetraammineruthenium(III) Chloride on Human Peripheral Blood Lymphocytes

Abstract

Chemotherapeutic agents play an important role in cancer treatment mostly due their systemic action on human organism allowing access to liquid tumors and even metastases. Among these drugs, ruthenium compounds have been showing promising results to treat tumors and represent an important development of new antitumor therapy. This study presents the evaluation of cis-(dichloro)tetraammineruthenium(III) chloride, cis-[RuCl(2)(NH(3))(4)]Cl, genotoxic effects using human peripheral blood lymphocytes cultured in vitro. Mitotic index (MI), chromosome aberrations (CA), and DNA damage using the comet assay were analyzed. MI in human peripheral blood lymphocyte cultures treated with 1, 10, 100, and 1,000 microg mL(-1) cis-[RuCl(2)(NH(3))(4)]Cl were 5.9%, 4.6%, 3.9%, and 0%, respectively. Doxorubicin chloridate was used as the positive control. CA derived from 1, 10, and 100 microg mL(-1) concentrations were defined as spontaneous when compared with the negative control, and at the concentration of 1,000 microg mL(-1), the cell cycle was inhibited (IM = 0%). Results obtained for the comet assay using cis-[RuCl(2)(NH(3))(4)]Cl suggest that this compound has no genotoxic activity against cultured human peripheral blood lymphocytes.

The ruthenium complex cis-(dichloro)tetrammineruthenium(III) chloride induces apoptosis and damages DNA in murine sarcoma 180 cells

“…Unlike the results of DNA damage presented in this study in S-180 cells, genotoxic studies using the alkaline version of the comet assay to evaluate the possible DNA-damaging effects of cis-[RuCl 2 (NH 3 ) 4 ]Cl in human peripheral blood lymphocytes (PBL) showed that this compound does not cause signifi cantly increased DNA damage in normal cells (Ribeiro et al 2009), suggesting that the genotoxic activity of this compound could be selective to tumour cells. Thus, it is possible that the cytotoxicity of cis-[RuCl 2 (NH 3 ) 4 ]Cl to several cancer cell lines in vitro (Silveira-Lacerda et al 2009) is partially due to its DNA damaging effects, as DNA damage is a potent stimulus for apoptotic cell death.…”

The Ruthenium Complex cis-(Dichloro)tetraammineruthenium(III) Chloride Presents Selective Cytotoxicity Against Murine B Cell Lymphoma (A-20), Murine Ascitic Sarcoma 180 (S-180), Human Breast Adenocarcinoma (SK-BR-3), and Human T Cell Leukemia (Jurkat) Tumor Cell Lines

“…Results of earlier studies show that cis-[RuCl 2 (NH 3 ) 4 ]Cl did not have genotoxic or clastogenic effects on cultured human PBL [47]. Even at concentrations above 1 mg mL −1 cis-[RuCl 2 (NH 3 ) 4 ]Cl, cultured human PBL presented inhibition of proliferation but not DNA breakage or chromosome aberrations.…”

“…The positive control, human PBL treated with doxorubicin at 0.2μg mL −1 , presented DNA damage, especially in class 4 [47].…”

A ruthenium(II) complex inhibits tumor growth in vivo with fewer side-effects compared with cisplatin

“…As a consequence, chemotherapy may lead to a second neoplasia [45]. The micronucleus test is a sensitive test which could detect the potential genotoxic complexes.…”