ArticleChemical research in toxicology2019
Induction of the Antioxidant Response by the Transcription Factor NRF2 Increases Bioactivation of the Mutagenic Air Pollutant 3-Nitrobenzanthrone in Human Lung Cells.
Article in Chemical research in toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Role of Human Aldo-Keto Reductases and Nuclear Factor Erythroid 2-Related Factor 2 in the Metabolic Activation of 1,8-Dinitropyrene and Its Metabolite 1-Amino-8-nitropyrene via Nitroreduction in Human Lung Cells.Chemical research in toxicology · 2025Article
- Radioactive Tracing of Testosterone Reveals Minimal Formation of 5α-DHT in SGBS Cells and Human Primary Adipocytes.Journal of the Endocrine Society · 2025Article
- Aldo-keto reductase (AKR) superfamily website and database: An update.Chemico-biological interactions · 2024Article
- The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis.Molecules and cells · 2023Review
- Role of Human Aldo-Keto Reductases and Nuclear Factor Erythroid 2-Related Factor 2 in the Metabolic Activation of 1-Nitropyrene via Nitroreduction in Human Lung Cells.Chemical research in toxicology · 2023Article
- Nitroreduction: A Critical Metabolic Pathway for Drugs, Environmental Pollutants, and Explosives.Chemical research in toxicology · 2022Review
- Intervening Effects and Molecular Mechanism of Quercitrin on PCV2-Induced Histone Acetylation, Oxidative Stress and Inflammatory Response in 3D4/2 Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Genetic and epigenetic regulation of the NRF2-KEAP1 pathway in human lung cancer.British journal of cancer · 2022Review
- AKR1C1 connects autophagy and oxidative stress by interacting with SQSTM1 in a catalytic-independent manner.Acta pharmacologica Sinica · 2022Article
- Peroxisome Proliferator-Activated Receptor-Gamma (PPAR-ɣ): Molecular Effects and Its Importance as a Novel Therapeutic Target for Cerebral Ischemic Injury.Neurochemical research · 2021Review
- Aldo-Keto Reductases and Cancer Drug Resistance.Pharmacological reviews · 2021Review
- Modulating glutathione thiol status alters pancreatic β-cell morphogenesis in the developing zebrafish (Danio rerio) embryo.Redox biology · 2021Article
- Nitrative DNA damage in lung epithelial cells exposed to indium nanoparticles and indium ions.Scientific reports · 2020Article
- Human aldo-keto reductases (AKR1C1-AKR1C3) increase the mutagenicity of environmental nitroarenes in the mammalian HPRT forward gene mutagenicity assay.Mutation research. Genetic toxicology and environmental mutagenesisArticle
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
3-Nitrobenzanthrone (3-NBA) is a suspected human carcinogen present in diesel exhaust. It requires metabolic activation via nitroreduction in order to form DNA adducts and promote mutagenesis. We have determined that human aldo-keto reductases (AKR1C1-1C3) and NAD(P)H:quinone oxidoreductase 1 (NQO1) contribute equally to the nitroreduction of 3-NBA in lung epithelial cell lines and collectively represent 50% of the nitroreductase activity. The genes encoding these enzymes are induced by the transcription factor NF-E2 p45-related factor 2 (NRF2), which raises the possibility that NRF2 activation exacerbates 3-NBA toxification. Since A549 cells possess constitutively active NRF2, we examined the effect of heterozygous (NRF2-Het) and homozygous NRF2 knockout (NRF2-KO) by CRISPR-Cas9 gene editing on the activation of 3-NBA. To evaluate whether NRF2-mediated gene induction increases 3-NBA activation, we examined the effects of NRF2 activators in immortalized human bronchial epithelial cells (HBEC3-KT). Changes in AKR1C1-1C3 and NQO1 expression by NRF2 knockout or use of NRF2 activators were confirmed by qPCR, immunoblots, and enzyme activity assays. We observed decreases in 3-NBA activation in the A549 NRF2 KO cell lines (53% reduction in A549 NRF2-Het cells and 82% reduction in A549 NRF2-KO cells) and 40-60% increases in 3-NBA bioactivation due to NRF2 activators in HBEC3-KT cells. Together, our data suggest that activation of the transcription factor NRF2 exacerbates carcinogen metabolism following exposure to diesel exhaust which may lead to an increase in 3-NBA-derived DNA adducts.
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