Comparative study on the induction of complex genomic alterations after exposure of mammalian cells to carboplatin and oxaliplatin

Abstract

Metal complexes are still broadly used as the first line of the treatment for different types of tumors nowadays. Carboplatin and oxaliplatin were authorized for clinical use, even though there is little information on the mutagenic profile associated to their usage. This study evaluated the cytostatic effects and the induction of complex genomic alterations after 24-h treatment of CHO-K1 cells to concentrations of 12.5–800 μM of carboplatin and oxaliplatin in the cytokinesis-block micronucleus assay (CBMN-Cyt). The results demonstrated that carboplatin and oxaliplatin significantly increased the frequency of micronuclei (MN), nucleoplasmatic bridges (NPBs), and nuclear buds (NBUDs). On one hand, oxaliplatin induces significantly more chromosomal abnormalities than carboplatin at concentrations of 12.5 and 25 μM. On the other hand, carboplatin, in cells exposed to concentrations of 50 and 100 μM, is more efficient than oxaliplatin in the induction of chromosomal instability events. Both drugs cause significant reduction in the cytokinesis-block proliferation index, demonstrating their cytostatic effects at concentrations 50–800 μM. The results of this study shed more light on the characterization of biological effects associated with the exposure to carboplatin and oxaliplatin.

Keywords:

• Platinum analogs
• cytostasis
• micronuclei
• nucleosplasmic bridge
• nuclear buds

Declaration of interest

The authors report that they have no conflicts of interest. This work was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, no. 855-25.51/13-4), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, no. 403582/2012-1), and Financiadora de Estudos e Projetos (FINEP).