Methyleugenol and oxidative metabolites induce DNA damage and interact with human topoisomerases
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2016 |
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Erschienen: |
2016 |
Enthalten in: |
Zur Gesamtaufnahme - volume:90 |
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Enthalten in: |
Archives of toxicology - 90(2016), 11 vom: 06. Nov., Seite 2809-2823 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Groh, Isabel Anna Maria [VerfasserIn] |
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Anmerkungen: |
Date Completed 06.03.2017 Date Revised 16.08.2019 published: Print-Electronic Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM254385303 |
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245 | 1 | 0 | |a Methyleugenol and oxidative metabolites induce DNA damage and interact with human topoisomerases |
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520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a DNA damage | |
650 | 4 | |a DNA double-strand breaks | |
650 | 4 | |a Methyleugenol | |
650 | 4 | |a Micronucleus induction | |
650 | 4 | |a Oxidative metabolites | |
650 | 4 | |a Topoisomerase inhibition | |
650 | 7 | |a 3'-oxomethylisoeugenol |2 NLM | |
650 | 7 | |a Biomarkers, Tumor |2 NLM | |
650 | 7 | |a Carcinogens, Environmental |2 NLM | |
650 | 7 | |a Epoxy Compounds |2 NLM | |
650 | 7 | |a H2AX protein, human |2 NLM | |
650 | 7 | |a Histones |2 NLM | |
650 | 7 | |a Mutagens |2 NLM | |
650 | 7 | |a Neoplasm Proteins |2 NLM | |
650 | 7 | |a Recombinant Proteins |2 NLM | |
650 | 7 | |a Topoisomerase I Inhibitors |2 NLM | |
650 | 7 | |a methyleugenol-2',3'-epoxide |2 NLM | |
650 | 7 | |a methyleugenol |2 NLM | |
650 | 7 | |a 29T9VA6R7M |2 NLM | |
650 | 7 | |a Eugenol |2 NLM | |
650 | 7 | |a 3T8H1794QW |2 NLM | |
650 | 7 | |a DNA Topoisomerases, Type I |2 NLM | |
650 | 7 | |a EC 5.99.1.2 |2 NLM | |
650 | 7 | |a TOP1 protein, human |2 NLM | |
650 | 7 | |a EC 5.99.1.2 |2 NLM | |
700 | 1 | |a Rudakovski, Olga |e verfasserin |4 aut | |
700 | 1 | |a Gründken, Malte |e verfasserin |4 aut | |
700 | 1 | |a Schroeter, Anika |e verfasserin |4 aut | |
700 | 1 | |a Marko, Doris |e verfasserin |4 aut | |
700 | 1 | |a Esselen, Melanie |e verfasserin |4 aut | |
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