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Mecanismos de lesao genetica por flavonoides

By Jorge Francisco Dias Rodrigues Gaspar


Epidemiological evidence associating red wine consumption with an increase in the incidence of gastric cancer prompted us to study the genotoxicity of this product. Data in the scientific literature is controversial and does not clearly identify the nature and origin of the compounds responsible for this genotoxicity. Results from our research work show that the genotoxic activity observed in the Ames test is due to the presence of quercetin and its glycosides, and the genotoxic activity of the final product is dependent on the vinification process. The genotoxic activity of quercetin in the Ames test, is increased in the presence of S9 and S100. Metabolization of this compound by each of these fractions seems to produce different reactive products to DNA. On the other hand, at pH values slightly higher than neutrality, this molecule autooxidizes, producing various reactive oxygen species (O_2"-, H_2O_2 and OH), which were shown to be responsible for the induction of breaks in plasmidic DNA in vitro. Apart from the genotoxic activity of red wine, due to its content in quercetin, we observed that both red and white wines were also genotoxic upon reaction with the nitrite ion at acidic pH values. Some of the precursors responsible for that activity were identified in red wine (malvidine-3-glycoside, quercetin and tyramine). Flavonoids are widely present in vegetables used in the human diet. We identified the flavonoids quercetin and malvidine-3-glycoside as genotoxic upon nitrosation and these results led us to study the presence of a similar activity in other flavonoids. We were able to identify the structural requirements for the genotoxic activity after nitrosation, namely the presence of OH groups in the B ringAvailable from Fundacao para a Ciencia e a Tecnologia, Servico de Informacao e Documentacao, Av. D. Carlos I, 126, 1200 Lisboa / FCT - Fundação para o Ciência e a TecnologiaSIGLEPTPortuga

Topics: 06V - Genetics, cytology, molecular biology
Year: 1994
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Provided by: OpenGrey Repository
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