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Ozone-Induced DNA Damage: A Pandora’s Box of Oxidatively Modified DNA Bases

2021· article· en· W3118623710 on OpenAlexafffund
J. Richard Wagner, Guru S. Madugundu, Jean Cadet

Bibliographic record

VenueChemical Research in Toxicology · 2021
Typearticle
Languageen
FieldEnvironmental Science
TopicAir Quality and Health Impacts
Canadian institutionsUniversité de Sherbrooke
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsChemistryDeoxyribonucleosidesDNAPyrimidineOzonolysisCytosineDNA damageBiochemistryDNA oxidationStereochemistryOrganic chemistry

Abstract

fetched live from OpenAlex

Ozone is a major component of air pollution and carries potentially mutagenic and harmful affects to health. The oxidation of isolated calf thymus DNA (CT-DNA) led to the nearly quantitative loss of normal DNA 2′-deoxyribonucleosides in the following order: T > G > C ≫ A. The major modification of pyrimidines (T, C, and 5-methylcytosine (5mC)) was the corresponding 5-hydroxyhydantoin derivative after complete digestion of DNA to its component 2′-deoxyribonucleosides. The oxidation of 5mC was 2.5-fold more susceptible than C considering the relative mole fraction of 5mC to C in CT-DNA. Other common oxidation products of pyrimidines (e.g., 5,6-dihydroxy-5,6-dihydropyrimidines, the so-called pyrimidine 5,6-glycols) were formed with a lower yield than 5-hydroxyhydantoin derivatives. In addition, several common oxidation products of G were observed (e.g., 8-oxo-7,8-dihydroguanine (8oxoG)) albeit with relatively minor yields. The sum of individual products was notably less than the loss of 2′-deoxyribonucleosides from which they were derived. In a search for additional products, we discovered the formation of pyrimidine ring fragments, predominantly N-formamide and N-urea, which were measured as a dinucleotide next to a nonmodified nucleotide upon partial digestion of oxidized DNA. Interestingly, the latter fragments were also observed in dinucleotides containing 8oxoG, indicating the formation of tandem lesions during ozonolysis of DNA. The oxidation of DNA upon exposure to ozone can be explained by reactions of an intermediate ozonide. These studies underline the complexity of ozone-induced DNA damage and provide valuable information to assess the formation of this damage in cellular DNA.

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)0.002
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
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 score0.024
Threshold uncertainty score0.998

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.004
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 science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.249
GPT teacher head0.450
Teacher spread0.201 · 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.

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

Citations26
Published2021
Admission routes2
Has abstractyes

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