On the mechanisms of genotoxicity and metabolism of quercetin.
Quercetin has been the subject of numerous studies on its genetic toxicity and carcinogenicity. Despite its well-proven genetic damaging activity for various genetic end-points (reverse mutations, induction of SOS functions, induction of sister chromatid exchanges, chromosomal aberrations and micronuclei), the mechanisms of genetic damage by quercetin remain, by and large, unknown. The present study aims to further extend the observations on the possible active oxygen species mediated DNA-damaging activity of quercetin and the role of cytochrome P450-dependent metabolism on the genotoxicity of quercetin. The results reported in this work show that quercetin can produce the OH. radical, as assessed by deoxyribose degradation in the presence of Fe3+/EDTA (ethylenediaminetetraacetic acid), and that it induces strand breakage in isolated plasmidic DNA (pUC18). The data support the hypothesis that the production of OH. is mediated by H2O2. The results with genetically engineered V79 cells expressing rat cytochromes 1A1, 1A2 and 2B1 failed to demonstrate metabolism of quercetin, as indicated by the fact that neither an enhancement nor a decrease in the genotoxicity of quercetin was observed. Results obtained on the pH dependence of the induction of chromosomal aberrations by quercetin in V79 cells show that, as the pH value of the medium is increased to 8.0, there is a significant increase in the number of aberrant cells, as expected if oxygen radicals are responsible for the formation of chromosomal aberrations.
Department of Genetics, Faculty of Medical Sciences UNL, Lisbon, Portugal.
J
J
Gaspar
A
A
Rodrigues
A
A
Laires
F
F
Silva
S
S
Costa
M J
MJ
Monteiro
C
C
Monteiro
J
J
Rueff
D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D003855:Deoxyribose / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D005818:Genetic Engineering; D006863:Hydrogen-Ion Concentration; D009153:Mutagens / Q000378:metabolism* / Q000494:pharmacology*; D011794:Quercetin / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D009153:Mutagens; D017382:Reactive Oxygen Species; D003855:Deoxyribose; D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin