Abstract #1692: Sulfhydryl-modulated mechanisms of the cytotoxicity of cadmium and inhibition of DNA topoisomerase II\#945;
Bibliographic record
Abstract
Cadmium (Cd 2+ ) is a highly toxic carcinogenic metal that is an environmental and occupational hazard. It also causes severe damage to many organs including the liver, kidney and lung. The molecular and cellular mechanisms responsible for its toxicity and carcinogenicity are not known. In this study we showed that divalent cadmium chloride strongly inhibited the DNA decatenation catalytic activity of human topoisomerase II\#945; (topo II) in the low micromolar concentration range. However, cadmium did not stabilize the DNA-topo II covalent complex, and thus may not act as a topo II poison. We also showed that cadmium inhibited the growth of human erythroleukemic K562 and CHO cells in the low micromolar concentration range. The growth inhibitory effects of cadmium on K562 and K/VP.5 cells (an etoposide-resistant cell line containing one-fifth the topo II content of the parental K562 cells) were not significantly different; a result which also suggested that cadmium is not a topo II poison. We and others have shown that the catalytic activity of topo II is strongly inhibited by sulfhydryl-reactive compounds that react with critical topo II cysteine sulfhydryl groups. Divalent cadmium forms a strong complex with cysteine. Consistent with the idea that cadmium may have its cytotoxicity modulated by GSH levels, buthionine sulfoximine (BSO) pretreatment to decrease GSH levels resulted in a greatly increased cadmium-induced cytotoxicity in K562 cells. Thus cellular GSH levels may be a key regulator of cellular toxicity of cadmium. The results of this study suggest that cadmium may exert some of its cell growth inhibitory and possibly its carcinogenic effects by inhibiting topo II through reaction with critical enzyme sulfhydryl groups. Support: CIHR and a Canada Research Chair in Drug Development. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1692.
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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 | 0.001 | 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 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".