Hormonal and genotoxic activity of resveratrol.
Resveratrol (RES) is a natural polyphenol present in red wines and various human food items. The estrogenic activity of RES was demonstrated in two in vitro assay systems, i.e. binding to human estrogen receptor alpha and stimulation of MCF-7 cell proliferation. To investigate the inhibition of cell proliferation observed at high concentrations of RES, we analyzed the compound for genotoxic potential. RES induced cellular toxicity, micronuclei, and metaphase chromosome displacement in L5178Y mouse lymphoma cells. Likewise, the induction of micronuclei was observed in Chinese hamster V79 cells. Determination of kinetochore signals in micronuclei and cell cycle analysis suggested that RES did not cause a direct disturbance of mitosis. In support of this notion, cell-free tubulin polymerization studies indicated no direct effect of RES on microtubule assembly. According to an estimation of daily intake and bioavailability, concentrations that were found genotoxic in vitro might be reached in human exposure. On the other side, the estrogenic acitivity might be beneficial. Therefore, further investigations of mechanisms, possibly including animal models, would be desirable to clarifiy a potential risk for humans.
Schmitt
E
E
Institute of Pharmacology and Toxicology, University of Würzburg, Germany.
Lehmann
L
L
Metzler
M
M
Stopper
H
H
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D018386:Kinetochores / Q000187:drug effects; D008223:Lymphoma / Q000235:genetics; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D015162:Micronucleus Tests; D015394:Molecular Structure; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D013997:Time Factors; D014404:Tubulin / Q000187:drug effects; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D013267:Stilbenes; D014404:Tubulin; D016650:Fluorescein-5-isothiocyanate; D000077185:Resveratrol