ON THE MECHANISMS OF GENOTOXICITY AND METABOLISM OF QUERCETIN

Quercetin has been the subject of numerous studies on its genetic toxi city and carcinogenicity. Despite its well-proven genetic damaging act ivity for various genetic end-points (reverse mutations, induction of SOS functions, induction of sister chromatid exchanges, chromosomal ab errations and micronuclei), the mechanisms of genetic damage by querce tin remain, by and large, unknown. The present study aims to further e xtend the observations on the possible active oxygen species mediated DNA-damaging activity of quercetin and the role of cytochrome P450-dep endent metabolism on the genotoxicity of quercetin. The results report ed in this work show that quercetin can produce the OH. radical, as as sessed by deoxyribose degradation in the presence of Fe3+/EDTA (ethyle nediaminetetraacetic acid), and that it induces strand breakage in iso lated plasmidic DNA (pUC18). The data support the hypothesis that the production of OH. is mediated by H2O2. The results with genetically en gineered 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 in crease in the number of aberrant cells, as expected if oxygen radicals are responsible for the formation of chromosomal aberrations.