5-Bromodeoxyuridine Radiosensitization: Conformation-Dependent DNA Damage
Bibliographic record
Abstract
DNA structure has recently emerged as one of the key factors governing the ability of 5-bromodeoxyuridine (BrdU) to radiosensitize DNA. Here, we report the dependence of the specific damage induced by BrdU for different DNA conformations. Strand breaks are specific for B-form DNA, whereas A-DNA only undergoes formation of piperidine-sensitive DNA lesions. Interstrand cross-links are only found in semi-complementary B-DNA. DNA conformation was altered by gradually rehydrating lyophilized DNA samples, which induces an A- to B-form transition. These results were also validated by irradiating DNA in solution, in the presence or absence of 80% ethanol to induce an A- or B-form, respectively. Alkali-labile DNA lesions were revealed using hot piperidine to transform both base and sugar lesions into strand breaks. We also analyzed the location of damage as a function of DNA structure: piperidine-sensitive lesions were observed exclusively at the site of BrdU substitution, whereas strand breaks were able to migrate along the DNA strand, with a clear preference for the adenine 5' of the BrdU. Thus, not only the hybridization state but also the DNA conformation affect the degree of sensitization by BrdU by influencing the amount and type of damage produced. Although clinical trials using BrdU as a radiosensitizer have been disappointing up to this point, these new findings point to several key features of BrdU radiosensitization that may alter future radiotherapeutic studies.
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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 | 0.001 | 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".