Genetic damage caused by natural plant substance methyl eugenol - important repair mechanism in human cells decoded
The chemical compound methyl eugenol occurs naturally in aromatic plants such as basil and is absorbed into the human body through food. In the liver, the substance can be activated by enzymes and cause genetic damage. A research team at RPTU University Kaiserslautern-Landau (RPTU) led by toxicologist Jörg Fahrer has now elucidated crucial mechanisms by which cells recognize and repair such damage. The results were published in the renowned journal Cell Death & Disease published.
The substance methyl eugenol is a component of essential oils and is found in basil, tarragon, nutmeg and fennel, among others. If it enters the body through food, it can be converted into a reactive form in the liver, which causes chemical changes to the DNA. "These so-called methyl eugenol-derived DNA adducts have already been detected in human liver tissue," explains Professor Dr. Jörg Fahrer from the area of study Food Chemistry and Toxicology at RPTU. Despite the evidence of a possible carcinogenic effect, it was previously unclear whether and how this damage is repaired in human cells.
In order to clarify this question, a team led by Fahrer investigated various human cell models in which central DNA repair mechanisms were specifically switched off. Biochemical, cell biological, microscopic and bioanalytical methods were also used. Scientists from Nutritional Toxicology at the University of Jena and Molecular Genetics at the Erasmus University Medical Center Rotterdam were also significantly involved in the study, which was led by the RPTU. The interdisciplinary study was made possible by funding from the German Research Foundation (DFG).
The researchers were able to show that the DNA damage caused by methyl eugenol blocks transcription. This is a fundamental process in which genetic information is transcribed from DNA into messenger RNA - a crucial step for protein production in the cell. This process is carried out by an enzyme called RNA polymerase II. "We used high-resolution microscopy to visualize the incorporation of new, fluorescently labeled RNA building blocks. We were able to observe that the methyl eugenol-derived DNA adducts led to a decrease in newly formed RNA," explains Caroline Quartz, PhD student in the Fahrer research group and first author of the study. She was supported by Riccarda Walter and Lydia Hens, who carried out their Master's theses on this topic and are now also doing their doctorates in the working group at the Department of Chemistry.
"DNA reading machine" blocked - repair mechanism switched on
The research team was able to show that the blocking of RNA polymerase II by methyl eugenol-DNA adducts activates transcription-coupled nucleotide excision repair (TC-NER). In very simplified terms, this means Damage caused by methyl eugenol blocks the work of an important "DNA reading machine" in the cell - and this in turn initiates a repair mechanism.
This was demonstrated by switching off the genes Cockayne syndrome A (CSA) and B (CSB), which play an indispensable role in TC-NER. Jörg Fahrer explains the background: "Cockayne syndrome is a rare human hereditary disease that is caused by the loss of these genes. This leads to premature ageing, degeneration of the nervous system and malfunctions of internal organs such as the liver in those affected." In fact, cells without CSA or CSB were very sensitive to the methyl eugenol-derived DNA damage. On the one hand, this manifested itself in an increased instability of the genetic material, as the researchers were able to illustrate with the detection of so-called micronuclei, among other things. These are fragments of structures outside the cell nucleus that contain genetic material and are attributable to chromosome damage. [mk3.1]On the other hand, high levels of methyl eugenol-dependent DNA adducts led to the initiation of programmed cell death, or apoptosis.
Finally, the team was able to show that the methyl eugenol-induced DNA adducts are not repaired throughout the genome, but remain there to a certain extent. "In future, we want to better understand how the damage in non-transcribed areas of the DNA is tolerated and to what extent this contributes to permanent genetic changes," says Professor Fahrer, looking to the future.
Relevant not only for patients with Cockayne syndrome (CS)
The new findings are of great importance for people with impaired or defective TC-NER such as patients with Cockayne syndrome (CS). In these people, the regular consumption of spice plants containing methyleugenol, such as basil, could lead to a strong accumulation of DNA damage and thus trigger liver damage. In addition, there are structurally related compounds such as estragole in food and herbal medicines. These cause similar chemical changes to the DNA as methyl eugenol and could therefore increase liver toxicity in sensitive individuals. Jörg Fahrer's team is also conducting intensive research into this. The overall aim is to elucidate the underlying toxicity mechanisms and thus ensure the safety of food and drugs.
The current study:
Quartz C, Walter RS, Hens LE, Carlsson MJ, Vollmer AS, Llerena Schiffmacher DA, Pätzold N, Ackermann G, Heylmann D, Stegmüller S, Meabed M, Cartus AT, Amelio I, Richling E, Vermeulen W, Pines A, Khobta A and Fahrer J. Transcription-coupled nucleotide excision repair protects against genomic instability and cell death induced by the liver toxin methyleugenol. Cell Death Dis 17, 483 (2026). https://doi.org/10.1038/s41419-026-08853-4
Scientific contact person:
Prof. Dr. Jörg Fahrer
Area of study: Food Chemistry and Toxicology / Department of Chemistry
Phone: 0631 205-2974
E-mail: joerg.fahrer[@]chem.rptu.de
Further information can be found at