Abstract 3449: Tungsten induces DNA damage and alters growth of developing B lymphocytes
Bibliographic record
Abstract
Abstract Tungsten is used widely in modern life in everything from household goods to technologically advanced material. However, little is known about the consequences of tungsten exposure. The lack of information concerning the toxicities associated with tungsten has been highlighted recently when high tungsten levels were discovered at the sites of several pediatric leukemia clusters. In these clusters, the majority of the children developed acute lymphoblastoid leukemia of the preB lymphocyte subtype. Thus, we investigated whether tungsten exposure alters the growth of preB cells and defined signaling pathways induced by tungsten. We exposed a co-culture system of the BU-11 preB cell line grown on BMS2 stromal cells to tungsten at doses found at the sites of the leukemia clusters. Growth, cell cycle, and apoptosis were determined in both cell types. While no significant changes in any of these parameters were observed in the BMS2 stromal cells, tungsten treatment for 48 hours decreased the BU-11 cell number, which correlated with an accumulation of cells in G0/G1 and increased apoptosis. Unlike polycyclic aromatic hydrocarbons, tungsten induced apoptosis in BU-11 cells grown in rIL-7 and therefore, is independent of the stromal cell layer. These results were confirmed in primary murine bone marrow cultures and in human peripheral blood mononuclear cells. Tungsten can polymerize forming polytungstates in water and soil. Interestingly, these polytungstates are significantly more effective at inhibiting growth in BU-11 and BMS2 cells. In order to begin analysis of signaling pathways induced by tungsten, cDNA microarrays were performed in a leukemic cell line following 24 hours of tungsten treatment and integrated pathway analyses were performed. Genes involved in DNA damage and ER stress were highly upregulated following tungsten exposure and validated by qPCR. An increase in DNA damage was confirmed by COMET assay. These results suggest that the developing B lymphocyte population is sensitive to tungsten-induced toxicities and that tungsten exposure may contribute to leukemogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3449.
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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 | 0.001 | 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".