Keskin, F., Noone, H., Dickman, M.J. orcid.org/0000-0002-9236-0788 et al. (8 more authors) (2025) Bracken fern carcinogen, Ptaquiloside, forms a guanine 06- adduct in DNA. Journal of Agricultural and Food Chemistry, 73 (2). pp. 1053-1061. ISSN 0021-8561
Abstract
Bracken fern (Pteridium sp.) is a viable and vigorous plant with invasive potential, ingestion of which causes chronic illness and cancers in farm animals. Bracken is a suspected human carcinogen, and exposure can result from ingestion of bracken-contaminated water, dairy products, or meat derived from livestock grazing on bracken fern. Bracken is also consumed in the diets of some communities. Ptaquiloside (PTQ), a known bracken carcinogen, is an illudane-type glycoside that forms a highly reactive electrophile, PTQ dienone, known to produce N7-guanine and N3-adenine adducts in DNA. Here, we demonstrate for the first time that PTQ dienone also produces an O6-alkylguanine (O6-PTBguanine) in DNA. Since O6-alkylguanines in DNA can be mutagenic, this work provides a potential mechanistic link between PTQ exposure and carcinogenicity. O6-PTBguanine is poorly repaired by O6-methylguanine-DNA methyltransferase that acts on other O6-alkylguanines, further highlighting the potential risk of exposure to bracken and PTQ.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | MGMT; O6-alkylguanine; bracken fern; carcinogenicity; ptaquiloside |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematical and Physical Sciences The University of Sheffield > Faculty of Engineering (Sheffield) > School of Chemical, Materials and Biological Engineering The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Funding Information: | Funder Grant number ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL EP/P010075/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Jan 2025 11:14 |
Last Modified: | 21 Jan 2025 11:14 |
Published Version: | https://doi.org/10.1021/acs.jafc.4c07187 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/acs.jafc.4c07187 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221999 |