Factors affecting the mutagenic activity of quercetin for Salmonella typhimurium TA98: metal ions, antioxidants and pH.
The mutagenic activity of quercetin for Salmonella typhimurium TA98 was inhibited by addition of metal salts. MnCl2 was a potent inhibitor, followed by CuCl2, FeSO4, and FeCl3, the probable mechanism being facilitated catalytic oxidation of quercetin. With quercetin incorporated at a level of 100 nmoles/plate, approximate doses (nmoles/plate) to give 50% inhibition of mutagenic activity were: MnCl2 less than 10 (-S9), 18 (+S9); CuCl2 65 (-S9), greater than 100 (+S9); FeSO4 190 (-S9), greater than 300 (+S9); or FeCl3 275 (-S9), greater than 300 (+S9). Ascorbate, superoxide dismutase, and, to a lesser extent, NADH and NADPH, all enhanced the mutagenic activity of quercetin in the absence of the mammalian-microsome (S9) system, but had no significant effect in the presence of the S9 mix. The maximum enhancement of activity by ascorbate or superoxide dismutase was approximately 87% of the increase achieved by addition of the S9 mix. Tyrosinase (catechol oxidase) substantially reduced the mutagenic activity of quercetin in the absence of the S9 mix. At lower levels of tyrosinase, activity was restored by incorporation of the S9 mix. It is proposed that the S9 mix enhances the mutagenic activity of quercetin by scavenging superoxide radicals, thus inhibiting the autoxidation of quercetin, and possibly by reducing quinone oxidation products of quercetin. The mutagenic activity of quercetin increased substantially when the pH of the media was decreased. This may be due in part to a decrease in ionization of quercetin at lower pH, thereby increasing its absorption by the tester strain, to a decrease in the rate of autoxidation of quercetin at lower pH, or to a combination of these.
D000975:Antioxidants; D001711:Biotransformation; D002374:Catalase / Q000378:metabolism; D005419:Flavonoids / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D008670:Metals; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction; D011794:Quercetin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D005419:Flavonoids; D008670:Metals; D011794:Quercetin; D002374:Catalase; D014442:Monophenol Monooxygenase; D013482:Superoxide Dismutase