Base excision repair of reactive oxygen species–initiated 7,8-dihydro-8-oxo-2′-deoxyguanosine inhibits the cytotoxicity of platinum anticancer drugs
Bibliographic record
Abstract
Anticancer therapy with cisplatin and oxaliplatin is limited by toxicity and onset of tumor resistance. Both drugs form platinum-DNA cross-linked adducts, and cisplatin causes oxidative DNA damage including the 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) lesion. To assess oxidative DNA damage as a mechanism of cisplatin and oxaliplatin cytotoxicity, 8-oxodG-directed base excision repair was stably enhanced in human embryonic kidney cells by FLAG-tagged expression of human oxoguanine glycosylase 1 (alpha-OGG1) or its functional homologue, Escherichia coli formamidopyrimidine glycosylase (fpg). Both drugs increased reactive oxygen species and 8-oxodG levels, and cytotoxicity was decreased by antioxidant pretreatment. Ectopic expression of alpha-OGG1 or fpg in cell clones increased nuclear and mitochondrial 8-oxodG repair, and reduced death by reactive oxygen species initiators (H(2)O(2), menadione) and both platinum drugs. Exposure to oxaliplatin caused a more marked and sustained block of cell proliferation than exposure to cisplatin. We conclude that the 8-oxodG lesion is cytotoxic, and base excision repair a likely determinant of risk. The greater antitumor efficacy of oxaliplatin seems unrelated to oxidative DNA damage, suggesting a novel strategy for improving the therapeutic index in cancer therapy.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".