title: 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.
authors.affiliation: a Laboratories of Genetic Toxicity (TOXIGEN) and Cellular Toxic-Genetic Analysis , Post-graduation Program in Molecular and Cellular Biology Applied to Health, Lutheran University of Brazil (ULBRA) , Canoas , RS , Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Souza
authors.affiliation: a Laboratories of Genetic Toxicity (TOXIGEN) and Cellular Toxic-Genetic Analysis , Post-graduation Program in Molecular and Cellular Biology Applied to Health, Lutheran University of Brazil (ULBRA) , Canoas , RS , Brazil.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: a Laboratories of Genetic Toxicity (TOXIGEN) and Cellular Toxic-Genetic Analysis , Post-graduation Program in Molecular and Cellular Biology Applied to Health, Lutheran University of Brazil (ULBRA) , Canoas , RS , Brazil.
authors.forename: Rafael Rodrigues
authors.initials: RR
authors.lastname: Dihl
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016466:CHO Cells; D016190:Carboplatin / Q000009:adverse effects*; D002467:Cell Nucleus / Q000187:drug effects*; D053144:Cell Nucleus Shape / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D043171:Chromosomal Instability / Q000187:drug effects*; D003412:Cricetulus; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000009:adverse effects*; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D009994:Osmolar Concentration; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D009153:Mutagens; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin
keywords: Platinum analogs; cytostasis; micronuclei; nuclear buds; nucleosplasmic bridge