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Record W4399567599 · doi:10.1021/acs.estlett.4c00342

Biotransformation of 6PPD-quinone <i>In Vitro</i> Using RTL-W1 Cell Line

2024· article· en· W4399567599 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueEnvironmental Science & Technology Letters · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicATP Synthase and ATPases Research
Canadian institutionsGlobal Institute for Water SecurityUniversity of Saskatchewan
FundersFisheries and Oceans CanadaNatural Sciences and Engineering Research Council of CanadaGlobal Water FuturesUniversity of Saskatchewan
KeywordsBiotransformationQuinoneIn vitroChemistryCell cultureStereochemistryCombinatorial chemistryBiologyBiochemistryGenetics

Abstract

fetched live from OpenAlex

Urban stormwater runoff contains the tire-derived transformation product N -(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine-quinone (6PPD-quinone), which poses significant environmental risks due to its high toxicity toward certain salmonids. 6PPD-quinone biotransformation has been investigated to explain some of the stark interspecies differences in sensitivity across different fishes; however, the primary mechanisms of 6PPD-quinone biotransformation remain unclear. This work aimed to explore the toxicokinetics of 6PPD-quinone in immortalized rainbow trout ( Oncorhynchus mykiss ) liver cells (RTL-W1) to identify transformation products, using coexposure with different enzyme inhibitors and inducers. Using high-resolution mass spectrometry, we identified three phase I 6PPD-quinone transformation products, with phenyl ring hydroxylation dominating, followed by hydroxylation of the alkyl side chain, and an unknown transformation product after 4 h of exposure. Co-exposing RTL-W1 cells with α-naphthoflavone and quercetin greatly inhibited the biotransformation of 6PPD-quinone, revealing that CYP1A is primarily involved in phase I biotransformation. Hepatic clearance predicted from in vitro results was further verified based on isolated perfused trout liver experiments. Further studies are necessary on the biotransformation and kinetics of 6PPD-quinone and the detoxification pathways involved in a wide phylogenetic space in fishes.

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.

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 score0.004
Threshold uncertainty score0.434

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
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 head0.006
GPT teacher head0.248
Teacher spread0.241 · 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