ArticleCarcinogenesis2014
Role of CYP2A13 in the bioactivation and lung tumorigenicity of the tobacco-specific lung procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: in vivo studies using a CYP2A13-humanized mouse model.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Role of P450 enzymes of the Cyp2abfgs gene subfamilies in tobacco smoke-induced lung tumorigenesis in mice.Carcinogenesis · 2026Article
- Acceleration of infectious disease drug discovery and development using a humanized model of drug metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Luteolin Alleviates Oxidative Stress in Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke via Modulation of the TRPV1 and CYP2A13/NRF2 Signaling Pathways.International journal of molecular sciences · 2023Article
- Detection of Transgene Location in the CYP2A13/2B6/2F1-transgenic Mouse Model using Optical Genome Mapping Technology.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells.Molecules (Basel, Switzerland) · 2022Article
- Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway.International journal of molecular sciences · 2022Article
- Assessing cytochrome P450 function using genetically engineered mouse models.Advances in pharmacology (San Diego, Calif.) · 2022Review
- Genetic and Enzymatic Characteristics of CYP2A13 in Relation to Lung Damage.International journal of molecular sciences · 2021Review
- Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.Archives of toxicology · 2021Review
- Identification of Key Functional Modules and Immunomodulatory Regulators of Hepatocellular Carcinoma.Journal of immunology research · 2021Article
- HapMap-based study: CYP2A13 may be a potential key metabolic enzyme gene in the carcinogenesis of lung cancer in non-smokers.Thoracic cancer · 2019Article
- Effects of cellular differentiation in human primary bronchial epithelial cells: Metabolism of 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone.Toxicology in vitro : an international journal published in association with BIBRA · 2019Article
- P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- Carcinogens and DNA damage.Biochemical Society transactions · 2018Review
- Chemopreventive action of Imatinib, a tyrosine kinase inhibitor in the regulation of angiogenesis and apoptosis in rat model of lung cancer.Molecular and cellular biochemistry · 2018Article
- Cytochrome P450s and Alcoholic Liver Disease.Current pharmaceutical design · 2018Review
- Inhibition of human cytochromes P450 2A6 and 2A13 by flavonoids, acetylenic thiophenes and sesquiterpene lactones from Pluchea indica and Vernonia cinerea.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13.International journal of environmental research and public health · 2017Article
- Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity.Toxicological research · 2017Review
- Dietary Dihydromethysticin Increases Glucuronidation of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol in A/J Mice, Potentially Enhancing Its Detoxification.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
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6 authors at 2 institutions in 1 country.
Funding
Abstract
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is abundant in tobacco smoke, is a potent lung procarcinogen. The present study was aimed to prove that transgenic expression of human cytochrome P450 2A13 (CYP2A13), known to be selectively expressed in the respiratory tract and be the most efficient enzyme for NNK bioactivation in vitro, will enhance NNK bioactivation and NNK-induced tumorigenesis in the mouse lung. Kinetic parameters of NNK bioactivation in vitro and incidence of NNK-induced lung tumors in vivo were determined for wild-type, Cyp2a5-null and CYP2A13-humanized (CYP2A13-transgenic/Cyp2a5-null) mice. As expected, in both liver and lung microsomes, the loss of CYP2A5 resulted in significant increases in Michaelis constant (K m) values for the formation of 4-oxo-4-(3-pyridyl)-butanal, representing the reactive intermediate that can lead to the formation of O(6)-methylguanine (O(6)-mG) DNA adducts; however, the gain of CYP2A13 at a fraction of the level of mouse lung CYP2A5 led to recovery of the activity in the lung, but not in the liver. The levels of O(6)-mG, the DNA adduct highly correlated with lung tumorigenesis, were significantly higher in the lungs of CYP2A13-humanized mice than in Cyp2a5-null mice. Moreover, incidences of lung tumorigenesis were significantly greater in CYP2A13-humanized mice than in Cyp2a5-null mice, and the magnitude of the differences in incidence was greater at low (30mg/kg) than at high (200mg/kg) NNK doses. These results indicate that CYP2A13 is a low K m enzyme in catalyzing NNK bioactivation in vivo and support the notion that genetic polymorphisms of CYP2A13 can influence the risks of tobacco-induced lung tumorigenesis in humans.
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