title: Mutagenic potential of the isoflavone irilone in cultured V79 cells.
abstract: After consumption of red clover-based dietary supplements, plasma concentrations of the isoflavone irilone (IRI) equal that of the well-investigated daidzein. Since some isoflavones are genotoxic, the potential of IRI to induce mutations was investigated. Gene mutations were determined by hypoxanthine-guanine phosphoribosyltransferase (HPRT) assay and sequencing of mutant cDNA, chromosome and genome mutations by micronucleus assay complemented by immunochemical staining of centromere proteins and microtubules in cultured V79 cells. Cell proliferation was monitored by electronic cell counting, flow cytometry and fluorescence microscopy. IRI did not affect the mutant frequency in the Hprt locus but altered the mutation spectrum by increasing the proportion of deletions and decreasing that of base pair substitutions. Induction of chromosome mutations was supported by a slight but significant increase in the number of micronucleated cells containing chromosomal fragments despite activation of three cell cycle checkpoints possibly interfering with micronuclei formation. Moreover, IRI exhibited a strong aneugenic potential characterized by disrupted mitotic spindles, mitotic arrest, and asymmetrical cell divisions leading to chromosome loss, nuclear fragmentation as well as mitotic catastrophe. Thus, IRI might be another isoflavone to be taken into account in safety assessment of dietary supplements.
authors.affiliation: Institute of Pharmacy and Food Chemistry, Chair of Food Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Scheffler
authors.affiliation: Institute of Pharmacy and Food Chemistry, Chair of Food Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Albrecht
authors.affiliation: Institute of Pharmacy and Food Chemistry, Chair of Food Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Harald L
authors.initials: HL
authors.lastname: Esch
authors.affiliation: Institute of Pharmacy and Food Chemistry, Chair of Food Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. Electronic address: leane.lehmann@uni-wuerzburg.de.
authors.forename: Leane
authors.initials: L
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002503:Centromere / Q000187:drug effects / Q000378:metabolism; D003412:Cricetulus; D004252:DNA Mutational Analysis; D019587:Dietary Supplements / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007529:Isoflavones / Q000633:toxicity*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D007529:Isoflavones; D009153:Mutagens; C530234:irilone; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: Dietary supplements; Irilone; Isoflavone; Mutagenicity; Mutation spectrum