title: In vitro assessment of mutagenic and genotoxic effects of coumarin derivatives 6,7-dihydroxycoumarin and 4-methylesculetin.
abstract: Coumarins are naturally occurring compounds, widely distributed throughout the plant kingdom (Plantae), and possess important pharmacological properties, including inhibition of oxidative stress. In this context, newly synthesized coumarin compounds are being produced due to their potent antioxidant activities. Therefore, the aim of the present study was to determine the in vitro cytotoxic, mutagenic, and genotoxic effects of 6,7-dihydroxycoumarin (6,7-HC) and 4-methylesculetin (4-ME) using the Salmonella/microsome test and in cultured human lymphocytes the comet assay and micronucleus test. The three coumarin derivatives concentrations evaluated in comet and MN assays were 2, 8, and 32 μg/mL, selected through a preliminary trypan blue-staining assay. In the Ames test, the 5 concentrations tested were 62.5, 125, 250, 500, and 750 μg/plate. Positive (methyl methane-sulfonate, MMS) and negative (dimethyl sulfoxide, DMSO) control groups were also included in the analysis. Our results showed that 4-ME induced greater cytotoxicity at high concentrations than 6,7-HC. In addition, both compounds were not mutagenic in the Ames test and not genotoxic or clastogenic/aneugenic in cultured human lymphocytes.
authors.affiliation: a Programa de Pós-Graduação em Biologia Geral e Aplicada , Universidade Estadual Paulista (UNESP), Instituto de Biociências , Botucatu , São Paulo , Brazil.
authors.forename: Edson Luis
authors.initials: EL
authors.lastname: Maistro
authors.forename: Eduardo
authors.initials: E
authors.lastname: de Souza Marques
authors.forename: Rafael Palhano
authors.initials: RP
authors.lastname: Fedato
authors.forename: Flora
authors.initials: F
authors.lastname: Tolentino
authors.forename: Chayene de Andrade Cezário
authors.initials: Cde A
authors.lastname: da Silva
authors.forename: Marcela Stefanini Ferreira
authors.initials: MS
authors.lastname: Tsuboy
authors.forename: Flavia Aparecida
authors.initials: FA
authors.lastname: Resende
authors.forename: Eliana Aparecida
authors.initials: EA
authors.lastname: Varanda
mesh_terms: D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D018384:Oxidative Stress / Q000187:drug effects; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development; D014468:Umbelliferones / Q000633:toxicity*
chemical_list: D009153:Mutagens; D014468:Umbelliferones; C570020:4-methylesculetin; C007628:esculetin