Arsenic Trioxide (ATO<sup>III</sup>) Induces NAD(P)H Quinone Oxidoreductase 1 (NQO1) Expression in Hepatic and Extrahepatic Tissues of C57BL/6 Mice
Bibliographic record
Abstract
Arsenic trioxide (ATO III ) has emerged as a potent therapeutic agent for acute promyelocytic leukemia (APL), yet its clinical application is often limited by significant adverse effects. This study investigates the molecular mechanisms underlying ATO III ’s impact on cellular detoxification pathways, focusing on the regulation of NAD(P)H/quinone oxidoreductase (NQO1), a crucial enzyme in maintaining cellular homeostasis and cancer prevention. We explored ATO III ’s effects on NQO1 expression in C57BL/6 mice and Hepa-1c1c7 cells, both independently and in combination with 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD), a known NQO1 inducer. Our findings revealed that ATO III significantly increased NQO1 expression in hepatic and extrahepatic tissues, as well as in Hepa-1c1c7 cells, at mRNA, protein, and activity levels. This upregulation occurred both in the presence and absence of TCDD. Mechanistically, we demonstrated that ATO III promotes the nuclear translocation of both nuclear factor erythroid 2-related factor-2 (NRF2) and aryl hydrocarbon receptor (AHR) transcription factors. Furthermore, ATO III exposure increased antioxidant response element (ARE)-driven reporter gene activity, indicating a transcriptional mechanism of NQO1 induction. Notably, gene silencing experiments confirmed the critical roles of both NRF2 and AHR in mediating ATO III -induced NQO1 expression. In conclusion, ATO III exposure is found to upregulate the NQO1 enzyme through a transcriptional mechanism via AHR- and NRF2- dependent mechanisms, offering valuable insights into its therapeutic mechanisms.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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".