ArticlePharmacogenetics and genomics2011
Characterization of UDP-glucuronosyltransferase 2A1 (UGT2A1) variants and their potential role in tobacco carcinogenesis.
Article in Pharmacogenetics and genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study.Journal of the National Cancer Institute · 2014Trial
- Review
- Integrated clinical genomic analysis reveals xenobiotic metabolic genes are downregulated in meningiomas of current smokers.Journal of neuro-oncology · 2023Article
- The odorant metabolizing enzyme UGT2A1: Immunolocalization and impact of the modulation of its activity on the olfactory response.PloS one · 2021Article
- Altered Metabolism of Polycyclic Aromatic Hydrocarbons by UDP-Glycosyltransferase 3A2 Missense Variants.Chemical research in toxicology · 2020Article
- UDP-Glycosyltransferase 3A Metabolism of Polycyclic Aromatic Hydrocarbons: Potential Importance in Aerodigestive Tract Tissues.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Role of l- and d-Menthol in the Glucuronidation and Detoxification of the Major Lung Carcinogen, NNAL.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women.Cancer medicine · 2019Article
- Regulation of UGT2A1 by miR-196a-5p and miR-196b-5p.The Journal of pharmacology and experimental therapeutics · 2019Article
- Carbonyl reduction of NNK by recombinant human lung enzymes: identification of HSD17β12 as the reductase important in (R)-NNAL formation in human lung.Carcinogenesis · 2018Article
- Glucuronidation and UGT isozymes in bladder: new targets for the treatment of uroepithelial carcinomas?Oncotarget · 2017Review
- Urinary biomarkers of smokers' exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach.Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals · 2013Article
- The Human UDP-glucuronosyltransferase UGT2A1 and UGT2A2 enzymes are highly active in bile acid glucuronidation.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- High throughput liquid and gas chromatography-tandem mass spectrometry assays for tobacco-specific nitrosamine and polycyclic aromatic hydrocarbon metabolites associated with lung cancer in smokers.Chemical research in toxicology · 2013Article
- Importance of UDP-glucuronosyltransferases 2A2 and 2A3 in tobacco carcinogen metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Identification and functional characterization of a novel UDP-glucuronosyltransferase 2A1 splice variant: potential importance in tobacco-related cancer susceptibility.The Journal of pharmacology and experimental therapeutics · 2012Article
- Contributions of human enzymes in carcinogen metabolism.Chemical research in toxicology · 2012Review
- Characterization of dibenzo[a,l]pyrene-trans-11,12-diol (dibenzo[def,p]chrysene) glucuronidation by UDP-glucuronosyltransferases.Chemical research in toxicology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveTo examine UGT2A1 expression in human tissues, determine its glucuronidation activity against tobacco carcinogens, and assess the potential functional role of UGT2A1 missense single nucleotide polymorphisms on UGT2A1 enzyme activity.
methodsReverse transcription polymerase chain reaction and real time polymerase chain reaction were used to assess UGT2A1 gene expression in various human tissues. A glucuronidation assay measured by reverse phase ultra-performance liquid chromatography was used to determine UGT2A1 activity.
resultsUGT2A1 was expressed in aerodigestive tract tissues including trachea, larynx, tonsil, lung, and colon; no expression was observed in breast, whole brain, pancreas, prostate, kidney, liver, or esophagus. UGT2A1 exhibited highest expression in the lung, followed by trachea >tonsil >larynx >colon >olfactory tissue. Cell homogenates prepared from wildtype UGT2A1(75Lys308Gly) overexpressing HEK293 cells showed significant glucuronidation activity against a variety of polycyclic aromatic hydrocarbons including, 1-hydroxy-benzo(a)pyrene, benzo(a)pyrene-7,8-diol, and 5-methylchrysene-1,2-diol. No activity was observed in UGT2A1 overexpressing cell homogenate against substrates that form N-glucuronides, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), nicotine, or N-OH-2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (N-OH PhIP). A significant (P<0.05) decrease (approximately 25%) in glucuronidation activity (Vmax/KM) was observed against all polycyclic aromatic hydrocarbons substrates for the UGT2A1(75Lys308Gly) variant compared with homogenates from wildtype UGT2A1(75Lys308Gly); no activity was observed for cell homogenates overexpressing the UGT2A1 variant for all substrates tested.
conclusionThese data suggest that UGT2A1 is an important detoxification enzyme in the metabolism of polycyclic aromatic hydrocarbons within target tissues for tobacco carcinogens and functional polymorphisms in UGT2A1 may play a role in tobacco-related cancer risk.
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