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Record W2130409836 · doi:10.1093/toxsci/kfh200

TCDD Affects DNA Double Strand-Break Repair

2004· article· en· W2130409836 on OpenAlexaff
Cadia Chan

Bibliographic record

VenueToxicological Sciences · 2004
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA Repair Mechanisms
Canadian institutionsQueen's University
Fundersnot available
KeywordsChinese hamster ovary cellHomologous recombinationDNA damageMolecular biologyBiologyDNADNA repairCarcinogenesisAphidicolinGenome instabilityCell biologyGeneCell cultureGeneticsDNA synthesis

Abstract

fetched live from OpenAlex

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental toxicant, elicits a spectrum of deleterious biological responses including carcinogenesis. We hypothesize that TCDD exposure exerts its carcinogenicity, in part, by affecting the repair of DNA double strand breaks (DSBs) through homologous recombination (HR), mediated by the AhR signaling pathway. To investigate this hypothesis we used a Chinese hamster ovary (CHO) cell line (CHO 33) containing a neo direct repeat recombination reporter substrate to determine whether TCDD affects DNA DSB repair. The Saccharomyces cerevisiae mitochondrial endonuclease I-SceI was used to induce a site specific DSB within the upstream neo recombination substrate in the CHO 33 cells. The cells were then exposed to 500 pM of TCDD in the presence or absence of the AhR antagonist alpha-naphthoflavone (0.1 microM) for 24 h. Two weeks later HR frequencies were determined by counting the number of functional neo expressing, G418-resistant colonies per live cells plated. TCDD significantly increased HR frequency, demonstrating that it does in fact modulate the repair of DNA DSBs. Southern blot analysis of G418-resistant colonies using a cDNA neo probe determined that both gene conversion and gene deletion HR events occurred as a result of DNA DSB repair and TCDD exposure. Exposure of cells to alpha-naphthoflavone resulted in a significant decrease in TCDD-induced HR frequency. These results demonstrate that TCDD, potentially acting via the AhR, can modulate HR repair of DNA DSBs in CHO 33 cells.

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)0.001
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 score0.018
Threshold uncertainty score0.406

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
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 head0.026
GPT teacher head0.286
Teacher spread0.260 · 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
Published2004
Admission routes1
Has abstractyes

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