Dimethylmonothioarsinic acid (DMMTAV) induces NQO1 expression through coordinated activation of NRF2 and AHR pathways
Bibliographic record
Abstract
Dimethylmonothioarsinic acid (DMMTA V ), a potent toxic metabolite of arsenic, exhibits higher cytotoxicity than other arsenicals. This study investigates its influence on NAD(P)H:quinone oxidoreductase (NQO1) regulation in C57BL/6 mice and Hepa-1c1c7 cells. Mice were administered DMMTA V (6 mg/kg, IP) with or without TCDD (15 µg/kg, IP), and hepatic and extrahepatic tissues were analyzed for NQO1 expression. In vitro, Hepa-1c1c7 cells were treated with 0-2 µM DMMTA V in the presence and absence of TCDD (1 nM), and NQO1 levels were assessed over time. Western blot, real-time PCR, and ARE-luciferase assays determined protein and transcriptional regulation. DMMTA V upregulated NQO1 in liver tissues and induced a time-dependent increase in vitro, peaking at 12 hours. It enhanced TCDD-induced NQO1 expression and increased nuclear NRF2 and AHR levels, with peak accumulation at two hours. ARE-luciferase activity confirmed transcriptional activation. These findings reveal DMMTA V enhances NQO1 primarily via NRF2/AHR pathway activation, providing insight into cellular responses to thioarsenicals. • DMMTA V upregulates the basal and TCDD-inducible expression of NQO1 in hepatic tissue of C57BL/6 mice. • DMMTA V upregulates the basal and TCDD-inducible expression of NQO1 in Hepa-1c1c7 cells • DMMTA V promotes the nuclear accumulation of both nuclear factor erythroid 2-related factor-2 (NRF2) and aryl hydrocarbon receptor (AHR) transcription factors. • DMMTA V exposure induced antioxidant response element (ARE)-driven reporter gene activity. • DMMTA V has no effect on the NQO1 protein stability. • DMMTA V 's-induced effects on NQO1 occur primarily through transcriptional regulation rather than post-translational modifications.
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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 | 0.001 |
| 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".