Structurally Similar Mycotoxins Aflatoxin B1 and Sterigmatocystin Trigger Different and Distinctive High-Resolution Mutational Spectra in Mammalian Cells
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toxins-17-00112.pdf
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Author(s)
Thongararm, Pennapa
Chancharoen, Marisa
Suwanwong, Nutchapong
Ruchirawat, Somsak
Ruchirawat, Mathuros
Fedeles, Bogdan I.
Croy, Robert G.
Essigmann, John M.
Date Issued
February 27, 2025
Journal
Toxins
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Thongararm, P.; Chancharoen, M.; Suwanwong, N.; Ruchirawat, S.; Ruchirawat, M.; Fedeles, B.I.; Croy, R.G.; Essigmann, J.M. Structurally Similar Mycotoxins Aflatoxin B1 and Sterigmatocystin Trigger Different and Distinctive High-Resolution Mutational Spectra in Mammalian Cells. Toxins 2025, 17, 112.
Version
Final published version
Abstract
Aflatoxin B1 (AFB1) and sterigmatocystin (ST) are mycotoxins that pose significant threats to human and animal health owing to their mutagenic, carcinogenic, and toxic properties. They are structurally similar and widely believed to exert their biological effects via the generation of DNA-damaging epoxides at their respective terminal furan rings. Despite structural identity in the warhead portion of each toxin, this work shows that distal parts of each molecule are responsible for the distinctive mutational fingerprints seen in gptΔ C57BL/6J mouse embryo fibroblasts (MEFs). The two toxins differ structurally in the puckered cyclopentenone ring of AFB1 and in the planar xanthone functionality of ST. While both toxins mainly induce GC→TA mutations, the aforementioned differences in structure apparently trigger unique patterns of mutations, as revealed by high-resolution duplex sequencing of MEF genomes. AFB1 is more mutagenic than ST and displays its transversion mutations in a pattern with primary and secondary hotspots (underscored) in 5′-CGC-3′ and 5′-CGG-3′ contexts, respectively. ST displays a modest 5′-CGG-3′ hotspot while its other GC→TA transversions are more uniformly distributed in a pattern resembling established oxidative stress mutational spectra. This research delineates the mutational spectra of AFB1 and ST, establishing these patterns as possible early-onset biomarkers of exposure.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Center for Environmental Health Sciences
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DOI of Published Version
https://doi.org/10.3390/toxins17030112
