ReviewChemical research in toxicology2014
Human aldo-keto reductases and the metabolic activation of polycyclic aromatic hydrocarbons.
Review in Chemical research in toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
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- Building a predictive model for polycyclic aromatic hydrocarbon dosimetry in organotypically cultured human bronchial epithelial cells using benzo[Toxicology reports · 2025Article
- InhibitingBiomedicines · 2025Article
- Reactive oxygen species regulate adipose-osteogenic lineage commitment of human mesenchymal stem cells by modulating gene expression of C/EBP homology protein and aldo-keto reductase family 1 member A1.Cell & bioscience · 2025Article
- Particulate Matter-Induced Emerging Health Effects Associated with Oxidative Stress and Inflammation.Antioxidants (Basel, Switzerland) · 2024Review
- Aldo-keto reductase (AKR) superfamily website and database: An update.Chemico-biological interactions · 2024Article
- Exploring Synergistic Interactions between Natural Compounds and Conventional Chemotherapeutic Drugs in Preclinical Models of Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Complex roles for sulfation in the toxicities of polychlorinated biphenyls.Critical reviews in toxicology · 2024Review
- Lung cancer associated with combustion particles and fine particulate matter (PMBiochemical pharmacology · 2023Review
- Association of smoking and dietary polycyclic aromatic hydrocarbon exposure on the prevalence of metabolic syndrome in Korean adults.Journal of exposure science & environmental epidemiology · 2023Article
- Dynamic changes of DNA methylation induced by benzo(a)pyrene in cancer.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023Review
- Quantification of Plasma 8-Isoprostane by High-Performance Liquid Chromatography with Tandem Mass Spectrometry in a Case-Control Study of Lung Cancer.International journal of environmental research and public health · 2022Article
- Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance.International journal of molecular sciences · 2022Review
- Nematodes As Soil Stress Indicators for Polycyclic Aromatic Hydrocarbons: a Review.Helminthologia · 2022Article
- Genetic and epigenetic regulation of the NRF2-KEAP1 pathway in human lung cancer.British journal of cancer · 2022Review
- Natural Chromosome-Chromid Fusion across rRNA Operons in aMicrobiology spectrum · 2022Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Aldo-keto reductases (AKRs) are promiscuous NAD(P)(H) dependent oxidoreductases implicated in the metabolic activation of polycyclic aromatic hydrocarbons (PAH). These enzymes catalyze the oxidation of non-K-region trans-dihydrodiols to the corresponding o-quinones with the concomitant production of reactive oxygen species (ROS). The PAH o-quinones are Michael acceptors and can form adducts but are also redox-active and enter into futile redox cycles to amplify ROS formation. Evidence exists to support this metabolic pathway in humans. The human recombinant AKR1A1 and AKR1C1-AKR1C4 enzymes all catalyze the oxidation of PAH trans-dihydrodiols to PAH o-quinones. Many human AKRs also catalyze the NADPH-dependent reduction of the o-quinone products to air-sensitive catechols, exacerbating ROS formation. Moreover, this pathway of PAH activation occurs in a panel of human lung cell lines, resulting in the production of ROS and oxidative DNA damage in the form of 8-oxo-2'-deoxyguanosine. Using stable-isotope dilution liquid chromatography tandem mass spectrometry, this pathway of benzo[a]pyrene (B[a]P) metabolism was found to contribute equally with the diol-epoxide pathway to the activation of this human carcinogen in human lung cells. Evaluation of the mutagenicity of anti-B[a]P-diol epoxide with B[a]P-7,8-dione on p53 showed that the o-quinone produced by AKRs was the more potent mutagen, provided that it was permitted to redox cycle, and that the mutations observed were G to T transversions, reminiscent of those observed in human lung cancer. It is concluded that there is sufficient evidence to support the role of human AKRs in the metabolic activation of PAH in human lung cell lines and that they may contribute to the causation of human lung cancer.
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