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 o f these compounds have been shown to be genotoxic to prokaryotic and eukary otic cells. In this study we tried to establish the chemical features respo nsible for the genotoxicity of flavonols and to study the conditions that c an modulate their genotoxicity namely pH, the presence of antioxidants and metabolism. We assessed the induction of revertants in Salmonella typhimuri um 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 radic al 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 t hat after metabolic activation is transformed into a catechol or a pyrogall ol, are flavonols whose genotoxicity in eukaryotic cells depends on their a utooxidation. 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 clar ify the mechanisms and the conditions that mediate the biological effects o f flavonols before considering them as therapeutical agents. (C) 2000 Elsev ier Science Ireland Ltd. AU rights reserved.