Home    Comparison of the Ability of Myricetin and Quercetin to Modulate the Oxidative DNA Damage Induced by Heterocyclic Amines

The aim of the present study was to compare the ability of the myricetin and quercetin to modulate the oxidative DNA damage induced by 2-amino-3, 8- dimethylimidazo [4,5-f] quinoxaline (8-MeIQx), 2-amino- 3, 4, 8- trimethylimidazo [4, 5-f]-quinoxaline (4,8-diMeIQx) and 2-amino-1-methyl-6-phenyl-imidazo [4,5-b] pyridine (PhIP), in human hepatoma cells. DNA damage (strand breaks and oxidized purines/pyrimidines) was evaluated by the alkaline single-cell gel electrophoresis or comet assay. None of the myricetin and quercetin concentrations tested protected against 8-MeIQx, 4, 8-diMeIQx and PhIP-induced DNA strand breaks. The oxidized pyrimidines induced by 4, 8-diMeIQx and PhIP were reduced by myricetin but not by quercetin. Quercetin reduced the oxidized purines induced by 8-MeIQx and PhIP, while myricetin also reduced the induced by 4, 8-diMeIQx. One feasible mechanism by which myricetin and quercetin exert their protective effect towards HCAs-induced oxidative DNA could be related in part to the reduction of human CYP1A1. Another mechanism claimed to be responsible for the protective effect of myricetin and quercetin is the induction of phase II metabolizing enzymes such as UDP-glucuronyltrasferase (UGT). The ethoxyresorufin O-deethylation (CYP1A1) activity was moderately inhibited by myricetin, while little effect was observed by quercetin. On the contrary, quercetin showed the greatest increase on UDP-glucuronyltransferase activity. However, these are not the only mechanisms by which myricetin and quercetin exert their protective effect, other mechanisms such as stimulation of the repair of carcinogen-induced DNA damage and or the free radical scavenging efficiency have been also implicated. In conclusion, our results clearly indicate that myricetin was more efficient than quercetin to prevent DNA damage (oxidized purines and pyrimidines) induced by the three HCAs evaluated. This protective effect depends on the chemical structure of flavonoid and the mutagen studied.

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