Archives of Toxicology

, Volume 90, Issue 11, pp 2809–2823 | Cite as

Methyleugenol and oxidative metabolites induce DNA damage and interact with human topoisomerases

  • Isabel Anna Maria Groh
  • Olga Rudakovski
  • Malte Gründken
  • Anika Schroeter
  • Doris Marko
  • Melanie Esselen
Biologics
First Online:
Received:
Accepted:

Abstract

Methyleugenol is a substituted alkenylbenzene found in several herbs and spices. It is classified by the European Union’s Scientific Committee on Food as a genotoxic carcinogen. We addressed the biological mechanism of the genotoxic properties of methyleugenol and its oxidative metabolites. Methyleugenol and the oxidative metabolites significantly enhanced the DNA damage in human colon carcinoma cells (HT29). Methyleugenol did not affect the protein status of γH2AX, a biomarker of DNA double-strand breaks, whereas its metabolites methyleugenol-2′,3′-epoxide and 3′-oxomethylisoeugenol significantly increased the cellular phosphorylated H2AX level. Both of these metabolites also showed a significant induction of micronuclei in HT29 cells. Furthermore, we investigated whether topoisomerase interaction contribute to the observed effect on DNA integrity. Methyleugenol-2′,3′-epoxide and 3′-oxomethylisoeugenol inhibited the activity of recombinant topoisomerase I. In HT29 cells, neither methyleugenol nor the metabolites affected the level of topoisomerase protein bound to DNA, excluding a topoisomerase poisoning mode of action. In addition, 3′-oxomethylisoeugenol potently diminished the level of camptothecin-stabilized topoisomerase I/DNA intermediates and camptothecin-induced DNA strand breaks. In conclusion, it could be suggested that 3′-oxomethylisoeugenol may also interact with classical or food-borne topoisomerase I poisons, diminishing their poisoning effectiveness.

Keywords

Methyleugenol Oxidative metabolites DNA damage DNA double-strand breaks Topoisomerase inhibition Micronucleus induction 
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Notes

Acknowledgments

The study was supported by Boehringer Ingelheim Fonds which financed the research habitation at the University of Vienna by a travel grant. The study was also supported by the grant ES419/2-1 of the Deutsche Forschungsgemeinschaft.

Compliance with ethical standards

Conflict of interest

The authors declare there are no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Isabel Anna Maria Groh
    • 1
    • 2
  • Olga Rudakovski
    • 1
  • Malte Gründken
    • 3
  • Anika Schroeter
    • 2
  • Doris Marko
    • 2
  • Melanie Esselen
    • 3
  1. 1.Institute of ChemistryDivision of Food Chemistry and Toxicology, University of KaiserslauternKaiserslauternGermany
  2. 2.Department of Food Chemistry and ToxicologyUniversity of ViennaViennaAustria
  3. 3.Institute of Food ChemistryWestfälische Wilhelms-Universität MünsterMünsterGermany

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