p53 triggers mitochondrial apoptosis following DNA damage-dependent replication stress by the hepatotoxin methyleugenol.


Journal

Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092

Informations de publication

Date de publication:
29 11 2022
Historique:
received: 30 05 2022
accepted: 16 11 2022
revised: 15 11 2022
entrez: 29 11 2022
pubmed: 30 11 2022
medline: 2 12 2022
Statut: epublish

Résumé

Liver cancer is one of the most frequent tumor entities worldwide, which is causally linked to viral infection, fatty liver disease, life-style factors and food-borne carcinogens, particularly aflatoxins. Moreover, genotoxic plant toxins including phenylpropenes are suspected human liver carcinogens. The phenylpropene methyleugenol (ME) is a constituent of essential oils in many plants and occurs in herbal medicines, food, and cosmetics. Following its uptake, ME undergoes Cytochrome P450 (CYP) and sulfotransferase 1A1 (SULT1A1)-dependent metabolic activation, giving rise to DNA damage. However, little is known about the cellular response to the induced DNA adducts. Here, we made use of different SULT1A1-proficient cell models including primary hepatocytes that were treated with 1'-hydroxymethyleugenol (OH-ME) as main phase I metabolite. Firstly, mass spectrometry showed a concentration-dependent formation of N

Identifiants

pubmed: 36446765
doi: 10.1038/s41419-022-05446-9
pii: 10.1038/s41419-022-05446-9
pmc: PMC9708695
doi:

Substances chimiques

methyleugenol 29T9VA6R7M
Tumor Suppressor Protein p53 0
DNA Adducts 0
bcl-2-Associated X Protein 0
1'-(hydroxymethyl)eugenol DA6575YC8S
Carcinogens 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1009

Informations de copyright

© 2022. The Author(s).

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Auteurs

Max J Carlsson (MJ)

Division of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany.

Anastasia S Vollmer (AS)

Rudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, 35392, Giessen, Germany.
Department of Dermatology, University Medical Center, 69120, Heidelberg, Germany.

Philipp Demuth (P)

Division of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany.

Daniel Heylmann (D)

Rudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, 35392, Giessen, Germany.

Diana Reich (D)

Institute of Toxicology, University Medical Center, Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Caroline Quarz (C)

Division of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany.

Birgit Rasenberger (B)

Institute of Toxicology, University Medical Center, Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Teodora Nikolova (T)

Institute of Toxicology, University Medical Center, Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Thomas G Hofmann (TG)

Institute of Toxicology, University Medical Center, Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Markus Christmann (M)

Institute of Toxicology, University Medical Center, Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Julia A Fuhlbrueck (JA)

Division of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany.

Simone Stegmüller (S)

Division of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany.

Elke Richling (E)

Division of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany.

Alexander T Cartus (AT)

Division of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany.

Jörg Fahrer (J)

Division of Food Chemistry and Toxicology, Department of Chemistry, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany. fahrer@chemie.uni-kl.de.
Rudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, 35392, Giessen, Germany. fahrer@chemie.uni-kl.de.
Institute of Toxicology, University Medical Center, Johannes Gutenberg University Mainz, 55131, Mainz, Germany. fahrer@chemie.uni-kl.de.

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Classifications MeSH