The role of tungsten in modulating DNA double-strand break repair and class switch recombination
Bibliographic record
Abstract
Tungsten, a transition metal with widespread applications, is increasingly recognized as an environmental contaminant with potential health impacts. While tungsten exposure has been previously associated with increased DNA damage, its specific effects on DNA repair mechanisms remain poorly understood. Here, we found that tungsten alone did not induce DNA damage in vitro, as assessed by γ-H2AX phosphorylation. However, tungsten exacerbated DNA double-strand breaks induced by genotoxic agents, delayed γ-H2AX resolution, and induced cell cycle arrest. Mechanistically, GFP-based reporter assays revealed that tungsten impairs both homologous recombination (HR) and non-homologous end joining (NHEJ), which coincided with reduced recruitment of critical repair proteins, including BRCA1, 53BP1, and ATM at DSB sites. To assess functional consequences of impaired DNA repair due to tungsten exposure, we examined immunoglobulin (Ig) class switch recombination (CSR), a critical antibody diversification process reliant on the repair of DSBs. Using the CH12F3 B cell line, we showed that tungsten significantly impaired cytokine stimulated-CSR from IgM to IgA without affecting cell proliferation or activation-induced cytidine deaminase (Aicda) expression. Furthermore, ex vivo activation of splenic B cells confirmed that tungsten exposure inhibits CSR from IgM to IgG1, independent of cell proliferation. Together, these data indicate that tungsten exposure impairs canonical DSB repair pathways and CSR, highlighting the potential consequences for immune function upon environmental or occupational exposure to tungsten.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".