Elucidation of the mechanisms underlying the potentiation of cell killing by ionizing radiation in MCF-7 breast tumor cells by the vitamin D3 analog EB 1089
Bibliographic record
Abstract
4413 Background and Rationale: We have recently reported that MCF-7 breast tumor cells exposed to fractionated radiation (5 × 2Gy) undergo a senescence-like growth arrest that is succeeded by rapid recovery of proliferative capacity. exposure to the Vitamin D 3 analog EB 1089 (100nM) prior to irradiation converts the initial growth arrest response to cell death and profoundly reduces the rate of proliferative recovery (DeMasters et al, J Steroid Biochem Mol Biol. 2004; 92(5):365–74). The present studies were designed to elucidate the biochemical and molecular basis for the potentiating effects of EB 1089. experimental Approaches: The induction and repair of DNA damage were evaluated by alkaline unwinding and 53BP1 foci formation. Effects on c-myc protein levels were assessed by Western blotting and through the use of c-myc inducible cells. The generation of reactive oxygen was monitored by dichlorofluorescein diacetate (DCF) fluorescence. Results: DNA Damage Bulk DNA damage induced by ionizing radiation was repaired within 4 hours both in the absence and presence of EB 1089 treatment. Similarly, DNA double strand breaks were detected within 6 hours based on 53BP1 foci formation, and the decline of foci over a period of 48 hours was not attenuated with EB 1089. c-myc EB 1089 inhibited radiation-induced down-regulation of c-myc. However, blocking c-myc down-regulation in a doxocycline-inducible MCF-7 cell line did not interfere with the induction of senescence by radiation or promote cell death by radiation. Reactive oxygen EB 1089 increased radiation-induced reactive oxygen species (ROS) generation, an effect which was blocked by the free radical scavenger N-acetyl cysteine (NAC). Current studies are focused on determining the effects of inhibition of ROS generation on the radiosensitizing effects of EB 1089. Conclusions: These studies indicate that the ability of EB 1089 to sensitize breast tumor cells to cell killing by ionizing radiation is not due to increased radiation-induced DNA damage or inhibition of DNA repair. The effects of EB 1089 also do not appear to be mediated through interference with the suppression of c-myc expression. Our studies suggest that the increased generation of reactive oxygen may play a role in the enhanced response to radiation in breast tumor cells with prior exposure to the vitamin D 3 analog, EB 1089.
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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) | 0.001 | 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".