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The aflatoxin B1-induced imidazole ring-opened guanine adduct: high mutagenic potential that is minimally affected by sequence context
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  • Irina G. Minko,
  • Andrew Kellum, Jr,
  • Michael Stone,
  • R. Stephen Lloyd
Irina G. Minko
Oregon Health and Science University
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Andrew Kellum, Jr
Vanderbilt University Medical Center
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Michael Stone
Vanderbilt University Medical Center
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R. Stephen Lloyd
Oregon Health and Science University

Corresponding Author:[email protected]

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Consumption of foods contaminated with aflatoxin B1 (AFB1) is a recognized risk factor for developing hepatocellular carcinomas (HCCs). The mutational signature of AFB1 is characterized by high frequency G > T transversions in a limited subset of trinucleotide sequences. The 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B1 (AFB1-FapyGua) has been implicated as the primary DNA lesion responsible for AFB1-induced mutations. This study evaluated the mutagenic potential of AFB1-FapyGua in four contexts, including hot- and cold-spot sequences as apparent in the mutational signature. Vectors containing AFB1-FapyGua were replicated in primate cells and the products of replication were isolated and sequenced. Regardless of the sequence context, AFB1-FapyGua caused base substitutions at frequencies of ~ 80-90%, with G > T transversions being most common. Spectra of mutations were only slightly modulated by the sequence context. These data suggest that mechanism(s) defining sequence context-dependent distribution of AFB1-induced mutations likely operates prior to replication.
22 Feb 2023Submitted to Environmental and Molecular Mutagenesis
24 Feb 2023Submission Checks Completed
24 Feb 2023Assigned to Editor
24 Feb 2023Review(s) Completed, Editorial Evaluation Pending
27 Feb 2023Reviewer(s) Assigned
28 Mar 2023Editorial Decision: Revise Minor
25 Apr 20231st Revision Received
26 Apr 2023Submission Checks Completed
26 Apr 2023Assigned to Editor
26 Apr 2023Review(s) Completed, Editorial Evaluation Pending
08 Jun 2023Editorial Decision: Accept