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Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts leads to Increased, Induced Mutations in Critical Genes
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)||adjacent||Moderate||Ted Simon (send email)||Open for citation & comment||EAGMST Under Review|
Life Stage Applicability
Key Event Relationship Description
There is no direct information concerning insufficient or mis-repair of AFB1 promutagenic adducts leading directly to mutations in critical genes. It is well known, however, that in general when the repair of DNA adducts is either done incorrectly or is insufficient to remove the DNA adduct and correct the DNA sequence prior to DNA replication, a mutation at the site of the DNA adduct will result in the daughter cells upon DNA replication.
Evidence Supporting this KER
When DNA adducts are not repaired, mutations result if cell replication (and DNA synthesis) takes place.
Uncertainties and Inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
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