title: Genotoxic assessment of the copper chelated compounds Casiopeinas: Clues about their mechanisms of action.
abstract: Casiopeinas is the generic name of a group of copper chelated complexes designed to be used as antineoplastic. Some of these compounds have shown promising results, and in fact, one of them named Casiopeina III-ia has completed preclinical trials and is ready to start clinical phase I in Mexico. As part of the tests that have to be done to every molecule intended to be used in humans, bacterial assays are required because of their sensitivity, speed and reproducibility and among them, Ames test and the SOS Chromotest are widely used to evaluate DNA damage. With the aim to contribute to complete safety information related to genotoxicity and support the hypothesis about their mode of action, four different Casiopeinas (Cas II-gly, Cas III-Ea, Cas III-ia and Cas III-Ha) were tested for genotoxicity with these assays, as well as differential cytotoxicity upon Escherichia coli mutants defectives in some DNA repair mechanisms. However, although it is well known that these molecules produce DNA breakage, the results of the Chromotest and Ames test were negative. Despite this is controversial, a possible explanation is that there is a direct interaction between DNA and the Casiopeinas tested.
authors.affiliation: Departamento de Biología, Instituto Nacional de Investigaciones Nucleares, Carretera México Toluca S/N, La Marquesa, Ocoyoacac, Mexico. Electronic address: jorge.serment@inin.gob.mx.
authors.forename: Jorge
authors.initials: J
authors.lastname: Serment-Guerrero
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad 3000, México DF CP 04510, Mexico.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bravo-Gomez
authors.affiliation: Departamento de Biología, Instituto Nacional de Investigaciones Nucleares, Carretera México Toluca S/N, La Marquesa, Ocoyoacac, Mexico.
authors.forename: Eric
authors.initials: E
authors.lastname: Lara-Rivera
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad 3000, México DF CP 04510, Mexico.
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Azuara
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D017321:Clinical Trials, Phase I as Topic; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008800:Mexico; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D009942:Organometallic Compounds; D003300:Copper
keywords: Ames test; Casiopeinas; Copper chelates; Genotoxicity; SOS Chromotest