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Record W4404789710 · doi:10.1021/acs.est.4c07236

Dose-Related Mutagenic and Clastogenic Effects of Benzo[ <i>b</i> ]fluoranthene in Mouse Somatic Tissues Detected by Duplex Sequencing and the Micronucleus Assay

2024· article· en· W4404789710 on OpenAlexafffund
David M. Schuster, Danielle LeBlanc, Gu Zhou, Matthew J. Meier, Annette Dodge, Paul A. White, Alexandra S. Long, Andrew Williams, Cheryl A. Hobbs, A.-K. Diesing, Stephanie L. Smith‐Roe, Jesse J. Salk, Francesco Marchetti, Carole L. Yauk

Bibliographic record

VenueEnvironmental Science & Technology · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsCarleton UniversityHealth CanadaUniversity of Ottawa
FundersNational Institute of Environmental Health SciencesNatural Sciences and Engineering Research Council of CanadaNational Institutes of HealthCanada Research ChairsHealth CanadaUniversity of OttawaBurroughs Wellcome Fund
KeywordsClastogenFluorantheneSomatic cellMicronucleus testMicronucleusDuplex (building)BiologyGeneticsMolecular biologyToxicologyChemistryGeneToxicityDNA

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that originate from the incomplete combustion of organic materials. We investigated the clastogenicity and mutagenicity of benzo[ b ]fluoranthene (BbF), one of 16 priority PAHs, in MutaMouse males after a 28 day oral exposure. BbF causes robust dose-dependent increases in micronucleus frequency in peripheral blood, indicative of chromosome damage. Duplex sequencing (DS), an error-corrected sequencing technology, reveals that BbF induces dose-dependent increases in mutation frequencies in bone marrow (BM) and liver. Mutagenicity is increased in intergenic relative to genic regions, suggesting a role for transcription-coupled repair of BbF-induced DNA damage. At higher doses, the maximum mutagenic response to BbF is higher in liver, which has a lower mitotic index but higher metabolic capacity than BM; however, mutagenic potency is comparable between the two tissues. BbF induces primarily C:G > A:T mutations, followed by C:G > T:A and C:G > G:C, indicating that BbF metabolites mainly target guanines and cytosines. The mutation spectrum of BbF correlates with cancer mutational signatures associated with tobacco exposure, supporting its contribution to the carcinogenicity of combustion-derived PAHs in humans. Overall, BbF’s mutagenic effects are similar to benzo[ a ]pyrene, a well-studied mutagenic PAH. Our work showcases the utility of DS for effective mutagenicity assessment of environmental pollutants.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.017
Threshold uncertainty score0.785

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.002
GPT teacher head0.188
Teacher spread0.186 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations16
Published2024
Admission routes2
Has abstractyes

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