The oxidative stress response is region specific in organogenesis stage mouse embryos exposed to 5‐bromo‐2′‐deoxyuridine
Bibliographic record
Abstract
BACKGROUND: The exposure of mouse embryos to 5-bromo-2'-deoxyuridine (BrdU), a model teratogen, generates oxidative stress, induces c-Fos dependent activator protein-1 (AP-1) DNA binding activity, and causes skeletal malformations (Sahambi and Hales, 2006). The goal of this study was to test the hypothesis that the ability of BrdU to induce oxidative stress, rather than its incorporation into DNA per se, is responsible for triggering the ensuing malformations. To test this hypothesis, we examined the regional localization of BrdU incorporation, 8-oxoguanine (8-oxoG), a marker of oxidative stress, and c-Fos immunoreactivity in organogenesis stage mouse embryos exposed to a teratogenic dose of BrdU. METHODS: Timed pregnant CD1 mice received vehicle (saline) or BrdU (600 or 1000 mg/kg body weight) on gestation day 9. N-acetyl-L-cysteine, a glutathione precursor, was administered to GD 9 mice 2 hours before treatment with vehicle or BrdU to determine the impact of inhibiting the oxidative stress response. Embryos were excised 3 hours after BrdU treatment and processed for staining for BrdU incorporated into DNA, 8-oxoG, and c-Fos. RESULTS: BrdU incorporation, 8-oxoG adduct formation and c-Fos immunoreactivity were highest in the rostral and caudal developing tissues of BrdU-exposed embryos. Although preadministration of N-acetyl-L-cysteine at a dose that decreased BrdU teratogenicity dampened the oxidative stress response, it did not affect the incorporation of BrdU into DNA. CONCLUSIONS: These data show that rostral and caudal neuroepithelial cells are particularly susceptible to oxidative stress in the organogenesis-stage embryo.
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How this classification was reachedexpand
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 | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".