Kinetics of H2AX phosphorylation after exposure to cisplatin
Bibliographic record
Abstract
BACKGROUND: Cisplatin is a widely used cancer chemotherapeutic drug that causes DNA crosslinking and stimulates H2AX phosphorylation. Our goal was to assess the potential of gammaH2AX to help predict tumor response to cisplatin treatment. METHODS: The kinetics of cisplatin-induced DNA interstrand crosslinks was measured using the alkaline comet assay and compared with gammaH2AX formation and clonogenic cell survival in several DNA repair proficient or deficient human and rodent cell lines. RESULTS: The comet assay was effective in ranking cell lines according to their relative sensitivity to cisplatin based on reduced crosslink formation measured 6 h after drug exposure or by the failure of irs3 and UV41 cell lines to subsequently remove crosslinks. In comparison, the initial rate of phosphorylation of H2AX measured over the first 6 h after cisplatin treatment was unrelated to drug sensitivity or crosslinking proficiency. However, for proliferating cell cultures, the fraction of cells that retained gammaH2AX foci 24 h after cisplatin treatment was correlated with the fraction of cells that lost clonogenic potential (slope = 1.1, r(2) = 0.85). CONCLUSIONS: H2AX phosphorylation occurs in response to replication fork damage caused by cisplatin induced DNA lesions, probably interstrand crosslinks. Although early kinetics of gammaH2AX formation was uninformative, retention of gammaH2AX foci 24 h after treatment was shown to be a useful indicator of cell response to killing by cisplatin. However, for gammaH2AX to serve as an indicator of cell viability after cisplatin treatment, cells must have the opportunity to transit S phase during the recovery period.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".