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Structural requirements for mutagenicity of flavonoids upon nitrosation. A structure-activity study
1Department of Genetics, Faculty of Medical Sciences UNL, Lisbon, Portugal.
Abstract:
A wealth of promutagens can damage DNA provided metabolic/chemical reactions take place before an ultimate mutagen is formed. Nitrosation reactions are amongst those chemical reactions which may take place to render some chemical classes of promutagens as ultimate mutagens. Flavonoids are amongst chemicals which can be rendered mutagenic upon nitrosation. In this study, 22 flavonoids were tested in the Ames assay for their mutagenicity upon nitrosation and the respective structural requirements for nitrosation-dependent mutagenicity were established. Nitrosatable chemicals present in the diet may play a role in the aetiology of gastric cancer and flavonoids are amongst the common molecules present in a variety of food items. Flavonoids such as quercetin and catechin were predicted to be non-mutagenic upon nitrosation by the CASE methodology and were shown in this study to be strong nitrosatable mutagens.
Insights
Dietary flavonoids can become mutagens after nitrosation reactions. This study identified structural requirements for this mutagenicity, revealing common flavonoids like quercetin are potent mutagens, contrary to prior predictions.
Area of Science:
- * Biochemistry and molecular toxicology, focusing on DNA damage and chemical carcinogenesis.
- * Food science and nutrition, investigating dietary components and their health implications.
Background:
- * Promutagens require metabolic or chemical activation to become ultimate mutagens.
- * Nitrosation is a key chemical reaction that can activate promutagens, including certain flavonoids.
- * Flavonoids are common dietary compounds, and their potential role in gastric cancer aetiology warrants investigation.
Purpose of the Study:
- * To assess the mutagenicity of 22 different flavonoids following nitrosation.
- * To determine the specific structural features of flavonoids responsible for nitrosation-dependent mutagenicity.
- * To evaluate the accuracy of the CASE methodology in predicting flavonoid mutagenicity after nitrosation.
Main Methods:
- * Ames assay was employed to test the mutagenicity of 22 flavonoids after nitrosation.
- * CASE (Computer-Assisted Structure-Activity) methodology was used for in silico prediction.
- * Comparative analysis of predicted versus experimentally determined mutagenicity.
Main Results:
- * Several flavonoids demonstrated significant mutagenicity after nitrosation, contrary to CASE predictions.
- * Specific structural requirements for nitrosation-dependent mutagenicity were identified.
- * Flavonoids like quercetin and catechin, predicted as non-mutagenic, proved to be potent mutagens upon nitrosation.
Conclusions:
- * Flavonoids can be activated into mutagens through nitrosation, posing a potential risk.
- * The study established structure-activity relationships for nitrosation-dependent flavonoid mutagenicity.
- * Experimental findings challenge in silico predictions, highlighting the need for empirical testing of dietary compounds.