The impact of human superoxide dismutase 1 expression in a mouse model on the embryotoxicity of hydroxyurea
Bibliographic record
Abstract
BACKGROUND: Oxidative stress is hypothesized to mediate embryotoxicity during organogenesis, yet the reactive oxygen species involved are not defined. The superoxide oxygen radical is converted to hydrogen peroxide, a less reactive species, by superoxide dismutases (SODs). If superoxide is important in mediating embryotoxicity, increased SOD expression should protect embryos against insult. Exposure to hydroxyurea during organogenesis causes brain defects, cleft palate, tail anomalies, and limb defects; administration of D-mannitol, a free radical scavenger, ameliorates hydroxyurea embryotoxicity, suggesting that oxidative stress is important. To elucidate the role of superoxide in mediating hydroxyurea embryotoxicity, we assessed the impact of human SOD1 expression in a murine model. METHODS: hSOD1 hemizygous male mice, carrying the human SOD1 gene, were mated to wild-type or hSOD1 hemizygous females. Dams were treated on gestation day (GD) 9 with saline (control) or 400 (low) or 600 (high) mg/kg hydroxyurea (n = 8-13/group). Mice were euthanized on GD 18 and developmental toxicity was assessed. RESULTS: Exposure to hydroxyurea caused a dose-dependent increase in fetal deaths that was not affected by hSOD1 expression; hydroxyurea decreased fetal weights in litters from wild-type but not hemizygous dams. Hydroxyurea increased the incidence of external and skeletal malformations; fetuses from hemizygous dams treated with high-dose hydroxyurea had fewer malformations compared to wild-type dams. There was no correlation between embryonic phenotype and genotype or SOD activity. CONCLUSION: Maternal hSOD1 expression protected fetuses against malformations induced by hydroxyurea, providing evidence that superoxide plays a role in mediating the response of organogenesis stage embryos to this teratogen.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".