8‐Oxoguanine DNA Glycosylase (OGG1) Deficiency Exacerbates Doxorubicin‐Induced Cardiac Dysfunction
Bibliographic record
Abstract
Doxorubicin is an anthracycline widely used for the treatment of various cancers; however, the drug has a common deleterious side effect, namely a dose‐dependent cardiotoxicity. Doxorubicin treatment increases the generation of reactive oxygen species, which leads to oxidative stress in the cardiac cells and ultimately DNA damage and cell death. The most common DNA lesion produced by oxidative stress is 7,8‐dihydro‐8‐oxoguanine (8‐oxoguanine), and the enzyme responsible for its repair is the 8‐oxoguanine DNA glycosylase (OGG1), a base excision repair enzyme. Here, we show that the OGG1 deficiency has no major effect on cardiac function at baseline or with pressure overload; however, we found an exacerbation of cardiac dysfunction as well as a higher mortality in Ogg1 knockout mice treated with doxorubicin. Our transcriptomic analysis also showed a more extensive dysregulation of genes in the hearts of Ogg1 knockout mice with an enrichment of genes involved in inflammation. These results demonstrate that OGG1 attenuates doxorubicin‐induced cardiotoxicity and thus plays a role in modulating drug‐induced cardiomyopathy.
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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 | 0.000 |
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".