Reduction in cadmium‐induced toxicity and c‐Jun N‐terminal kinase activation by glutathione in cultured mouse embryonic cells
Bibliographic record
Abstract
INTRODUCTION: Cadmium (Cd(2+)) induces limb defects and other malformations in experimental animals. However, the mechanisms of the developmental toxicity of this metal are not fully understood. The ubiquitous intracellular tripeptide glutathione (GSH) protects nonembryonic cells from Cd(2+)-induced cell death and is essential for normal embryonic development. We predicted that pretreatment with GSH would prevent cytotoxicity in cultured mouse embryonic limb bud cells exposed to Cd(2+). Additionally, it was expected that GSH pretreatment would prevent the Cd(2+)-induced activation of the signaling molecule c-Jun N-terminal kinase (JNK), which becomes phosphorylated upon exposure to Cd(2+). METHODS: Primary micromass cultures of limb bud cells obtained from organogenesis-stage mouse embryos were treated with either Cd(2+) or GSH alone, or both Cd(2+) and GSH. Treatment with GSH commenced 4 hr prior to Cd(2+) treatment. RESULTS: Cell proliferation was inhibited by approximately 50% after exposure to 4 μM Cd(2+) for 5 days. Cd(2+) treatment also resulted in a dose-dependent increase in the intracellular GSH content as measured after 5 days of exposure. Pretreatment with 4 mM GSH for 4 hr prevented the Cd(2+)-induced inhibition of cell proliferation and differentiation and also inhibited a threefold activation of JNK induced by 4 μM Cd(2+) after 24 and 48 hr of exposure. CONCLUSION: Exogenous GSH protects cultured embryonic limb bud cells from Cd(2+)-induced inhibition of cell proliferation and differentiation, which is associated with the activation of JNK.
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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 | 0.002 | 0.001 |
| 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 | 0.001 |
| 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".