title: Genistein and delphinidin antagonize the genotoxic effects of the mycotoxin alternariol in human colon carcinoma cells.
abstract: Although associated with anti-oxidative properties, genistein has been reported to induce DNA strand breaks, whereby oxidative stress and topoisomerase poisoning are considered as potential mechanisms. In contrast, delphinidin, a catalytic topoisomerase inhibitor, is known to suppress the DNA-damaging properties of several topoisomerase poisons. Recently, alternariol, a mycotoxin produced by Alternaria spp., was found not only to induce oxidative stress but also to act as a topoisomerase poison. As both, polyphenols and mycotoxins, might occur in our nutrition simultaneously, the question was addressed whether potential combinatory effects on DNA integrity have to be considered.
  
  
  
  We determined combinatory effects of either genistein or delphinidin with alternariol in HT-29 cells. Cytotoxicity was assessed by WST-1 and SRB assays, whereby only weak interactions were observed. The comet assay revealed significant antagonistic interactions of both polyphenols with the genotoxicity of AOH. The underlying mechanism comprises the suppression of alternariol-mediated stabilization of DNA/topoisomerase-II-intermediates, as observed in the ICE assay. Furthermore, DEL but not GEN was found to suppress AOH-mediated oxidative stress.
  
  
  
  Our data indicate that a respective polyphenol-rich diet might aid to protect against genotoxic damages caused by AOH, whereby bioactive concentrations of DEL are predominantly expected locally in the intestines.
authors.affiliation: Faculty of Chemistry, Department of Food Chemistry and Toxicology, University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Aichinger
authors.affiliation: Faculty of Chemistry, Department of Food Chemistry and Toxicology, University of Vienna, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Beisl
authors.affiliation: Faculty of Chemistry, Department of Food Chemistry and Toxicology, University of Vienna, Vienna, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D020552:Comet Assay; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004336:Drug Antagonism; D019833:Genistein / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007783:Lactones / Q000633:toxicity*; D009152:Mutagenicity Tests; D009183:Mycotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D007783:Lactones; D009183:Mycotoxins; D017382:Reactive Oxygen Species; D019833:Genistein; D004250:DNA Topoisomerases, Type II; C017185:delphinidin; C005197:alternariol
keywords: Anthocyanin; Food contaminant; Genotoxicity; Oxidative stress; Synergism