<i>N</i>-OXIDATION OF AROMATIC AMINES BY INTRACELLULAR OXIDASES
Why this work is in the frame
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Bibliographic record
Abstract
The introduction includes a literature review of DNA reactive species and DNA adduct formation that results from aromatic amine N-oxidation catalyzed by hepatic cytochrome P450 vs. that catalyzed by nonhepatic peroxidases. Experimental evidence is then described for a novel oxidative stress mechanism involving prooxidant N-cation radical formation by both oxidases, which is proposed as a contributing mechanism for aromatic amine induced cytotoxicity and carcinogenesis. Aromatic amine N-cation radicals formed by peroxidases were found to cooxidize GSH or NADH and form reactive oxygen species. The latter could explain the reported DNA oxidative damage found in vivo following methylaminoazobenzene administration [Hirano et al. Analyses of Oxidative DNA Damage and Its Repair Activity in the Livers of 3'-Methyl-4-dimethylaminoazobenzene-Treated Rodents. Jpn. J. Cancer Res. 2000, 91, 681-685]. It was also found that the prooxidant activity of the aromatic amine increased as its redox potential, i.e., ease of oxidation decreased with o-anisidine and aminofluorene being the most effective at forming reactive oxygen species. This suggests that the rate-limiting step in the cooxidation is the rate of arylamine oxidation by the peroxidase. Incubation of hepatocytes with aromatic amines caused a decrease in the mitochondrial membrane potential before cytotoxicity ensued. The CYP1A2-induced hepatocytes isolated from 3-methylcholanthrene administered rats were much more susceptible to some arylamines and were protected by CYP1A2 inhibitors. Hepatocyte GSH was also depleted by all arylamines tested and extensive GSH oxidation occurred with o-anisidine and aminofluorene, which was prevented by CYP1A2 inhibitors. This suggests that in intact hepatocytes CYP1A2 may also catalyze a one-electron oxidation of some arylamines to form prooxidant cation radicals, which cooxidize GSH to form the reactive oxygen species.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it