title: Modulating effect of losartan potassium on the mutagenicity and recombinogenicity of doxorubicin in somatic cells of Drosophila melanogaster.
abstract: Losartan potassium is an antihypertensive drug in the angiotensin II receptor antagonist (ARA) class. Some studies claim that, in addition to regulating blood pressure, this class of drug has anticancer properties. The objective of this study was to evaluate the genotoxic and antigenotoxic potential of losartan potassium using the SMART (Somatic Mutation and Recombination Test) assay on the somatic cells of Drosophila melanogaster, as well as the possible modulating effects of this drug, when associated with doxorubicin (DXR). Third instar larvae, descendents of standard and high bioactivation (ST and HB) crosses, were chronically treated with different concentrations of losartan potassium (0.25; 0.5; 1; 2; and 4 mM) alone or in association (co-treatment) with doxorubicin (DXR 0.125 mg/mL). The results showed an absence of a mutagenic effect of losartan potassium. In the co-treatment of losartan with DXR, the results showed that losartan is capable of reducing the number of mutant spots induced by DXR without altering the recombinogenic effect of the chemotherapeutic agent. Antiproliferative action appears to be the main mechanism involved in reducing the frequency of mutant spots and consequent modulation of alterations induced by DXR, although this parameter has not been directly assessed in this study.
authors.affiliation: Universidade Federal de Uberlândia, Institute of Genetics and Biochemistry, Bloco 2E, Campus Umuarama, Uberlândia, Minas Gerais, Brazil; Centro Universitário de Patos de Minas, Laboratory for Cytogenetics and Mutagenesis, Patos de Minas, Minas Gerais, Brazil. Electronic address: rosianegomes2003@yahoo.com.br.
authors.forename: R G
authors.initials: RG
authors.lastname: Silva-Oliveira
authors.affiliation: Universidade Federal de Uberlândia, Institute of Genetics and Biochemistry, Bloco 2E, Campus Umuarama, Uberlândia, Minas Gerais, Brazil; Centro Universitário de Patos de Minas, Laboratory for Cytogenetics and Mutagenesis, Patos de Minas, Minas Gerais, Brazil.
authors.forename: P C
authors.initials: PC
authors.lastname: Orsolin
authors.affiliation: Universidade Federal de Uberlândia, Institute of Genetics and Biochemistry, Bloco 2E, Campus Umuarama, Uberlândia, Minas Gerais, Brazil; Centro Universitário de Patos de Minas, Laboratory for Cytogenetics and Mutagenesis, Patos de Minas, Minas Gerais, Brazil.
authors.forename: J C
authors.initials: JC
authors.lastname: Nepomuceno
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D004317:Doxorubicin / Q000633:toxicity*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000254:growth & development; D005260:Female; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D011995:Recombination, Genetic / Q000187:drug effects*; D014921:Wings, Animal / Q000187:drug effects / Q000254:growth & development
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D019808:Losartan
keywords: Drosophila melanogaster; Losartan potassium; Modulating effect; SMART