Chemical features of flavonols affecting their genotoxicity. Potential implications in their use as therapeutical agents.

Flavonls are natural compounds present in edible plants and possess several biological activities that can be useful in drug design. Conversely some of these compounds have been shown to be genotoxic to prokaryotic and eukaryotic cells. In this study we tried to establish the chemical features responsible for the genotoxicity of flavonols and to study the conditions that can modulate their genotoxicity namely pH, the presence of antioxidants and metabolism. We assessed the induction of revertants in Salmonella typhimurium TA98 and the induction of Chromosomal aberrations in V79 cells by eight different flavonols and one catechin in the presence and in the absence of metabolizing systems. We have also studied the generation of hydroxyl radical by these flavonoids using the deoxyribose degradation assay. The results obtained in this study suggest that flavonols having a free hydroxyl group at position 3 of the C ring, a free hydroxyl group at position 7 of the A ring and a B ring with a catechol or pyrogallol structure, or a structure that after metabolic activation is transformed into a catechol or a pyrogallol, are flavonols whose genotoxicity in eukaryotic cells depends on their autooxidation. These flavonols can autooxidize when the pH value is slightly alkaline, such as in the intestine, and therefore can induce genotoxicity in humans. Given the above mentioned considerations it is necessary to clarify the mechanisms and the conditions that mediate the biological effects of flavonols before considering them as therapeutical agents.

Mechanisms of myricetin mutagenicity in V79 cells: involvement of radicalar species.

Myricetin is a flavonol that is widely distributed in edible plants and although it has been proved to be genotoxic in bacteria and to induce significant concentration-dependent nuclear DNA degradation concurrent with lipid peroxidation, very little is known about its mechanisms of genotoxicity. In this work we tried to evaluate the role of rat cytochromes P450 in the genotoxicity of myricetin and to study the role that radicalar species may have in its mutagenicity. The results obtained show that the genotoxicity of myricetin as assessed by the induction of chromosomal aberrations is not different in V79 cells lines genetically engineered for the expression of rat cytochromes P450 1A1, 1A2, and 2B1, compared to parental cell lines. We have also been able to show that reactive oxygen species resulting from the autooxidation of myricetin at pH values above neutrality have an important role in its mutagenicity. Therefore, under some conditions, myricetin can act as a prooxidant.

[The prevention of hereditary erythrocytic diseases]. / Profilaxia das doenças hereditárias do eritrócito.

The authors report the importance of not only all over the world but also in Portugal and, particularly, in Dona Estefânia Hospital. Some considerations are made about the usefulness of molecular biology methods in prenatal diagnosis. With this tool can also be do the origins and migrations of populations, which contributes to the knowledge of aspects of our history. Finally, they present consensual attitudes which should adopt regarding these chronic diseases, with special emphasis to the prophylactic aspects.