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Genotoxicity of quercetin in cultured mammalian cells
Abstract:
The naturally occurring flavonol, quercetin, was investigated concerning its ability to induce SCEs and HGPRT-deficient mutants in V79 Chinese hamster cells, and HGPRT- and TK-deficient mutants in mouse lymphoma L5178Y cells. V79 cells were exposed to quercetin in monolayer, under exponential growing condition, in suspension in the presence of liver homogenate, and in co-cultivation with primary chick embryo hepatocytes. No induction of HGPRT-deficient mutants was observed. Furthermore, under standard conditions, no relevant increase in the number of SCEs could be detected. If, however, the cells were exposed simultaneously to quercetin and BrdUrd, a greater than 3-fold increase in the number of SCEs was observed. This induction was dose-related for both quercetin and BrdUrd. Treatment of L5178Y cells with quercetin did not result in an increase in HGPRT-deficient mutants. At the TK locus a weak increase in the number of TK-deficient mutants was found. Addition of liver homogenate abolished this effect. The inability of quercetin to induce SCEs and point mutations in mammalian cells, and the fact that the clastogenic effect of quercetin, whereby it induces TK-deficient mutants in mouse lymphoma L5178Y cells, is abolished by the addition of liver homogenate, may explain the negative outcome of the majority of carcinogenicity studies on quercetin in mammals.
Insights
Quercetin did not induce mutations in most tests, but it increased SCEs when combined with BrdUrd. Liver homogenate reduced quercetin's clastogenic effects, potentially explaining its negative carcinogenicity results.
Area of Science:
- Toxicology
- Genetics
- Biochemistry
Background:
- Quercetin is a naturally occurring flavonol with potential health benefits.
- Its genotoxic and mutagenic potential in mammalian cells requires thorough investigation.
Purpose of the Study:
- To evaluate quercetin's ability to induce SCEs and gene mutations in mammalian cells.
- To assess the influence of metabolic activation (liver homogenate) on quercetin's genotoxicity.
Main Methods:
- Exposure of V79 Chinese hamster cells and mouse lymphoma L5178Y cells to quercetin.
- Assays for sister chromatid exchanges (SCEs) and HGPRT/TK-deficient mutants.
- Inclusion of liver homogenate and BrdUrd in specific experimental conditions.
Main Results:
- Quercetin did not induce HGPRT-deficient mutants in V79 or L5178Y cells.
- A significant, dose-related increase in SCEs was observed only when quercetin was combined with BrdUrd.
- A weak increase in TK-deficient mutants in L5178Y cells was noted, but abolished by liver homogenate.
Conclusions:
- Quercetin exhibits limited genotoxic potential in mammalian cells under standard conditions.
- Its clastogenic effect is dependent on BrdUrd presence and is mitigated by metabolic activation.
- These findings may reconcile quercetin's in vitro genotoxicity with negative in vivo carcinogenicity data.