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http://ir.nhri.org.tw/handle/3990099045/5537
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Title: | Association of CYP2E1, GST and mEH genetic polymorphisms with urinary acrylamide metabolites in workers exposed to acrylamide |
Authors: | Huang, YF;Chen, ML;Liou, SH;Chen, MF;Uang, SN;Wu, KY |
Contributors: | Division of Environmental Health and Occupational Medicine |
Abstract: | This study elucidates the association of acrylamide metabolites, N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (GAMA2), and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA3) in urine with genetic polymorphisms of the metabolic enzymes cytochrome P450 2E1 (CYP2E1), microsomal epoxide hydrolase (mEH) in exon 3 and exon 4, glutathione transferase theta (GSTT1) and mu (GSTM1), involved in the activation and detoxification of acrylamide (AA) in humans. Eighty-five workers were recruited, including 51 AA-exposed workers and 34 administrative staffs serve as controls. Personal air sampling was performed for the exposed workers. Each subject provided pre- and post-shift urine samples and blood samples. Urinary AAMA, GAMA2 and GAMA3 levels were simultaneously quantified using liquid chromatography-electronspray ionization/tandem mass spectrometry (LC-ESI-MS/MS). CYP2E1, mEH (in exon 3 and exon 4), GSTT1, and GSTM1 were analyzed using polymerase chain reaction (PCR). Our results reveal that AA personal exposures ranged from 4.37x10(-3) to 113.61mug/m(3) with a mean at 15.36mug/m(3). The AAMA, GAMA2, and GAMA3 levels in the exposed group significantly exceeded those in controls. The GAMAs (the sum of GAMA2 and GAMA3)/AAMA ratios, potentially reflecting the proportion of AA metabolized to glycidamide (GA), varied from 0.003 to 0.456, and indicate high inter-individual variability in the metabolism of AA to GA in this study population. Multivariate regression analysis demonstrates that GSTM1 genotypes significantly modify the excretion of urinary AAMA and the GAMAs/AAMA ratio, exon 4 of mEH was significantly associated with the urinary GAMAs levels after adjustment for AA exposures. These results suggest that mEH and/or GSTM1 may be associated with the formation of urinary AAMA and GAMAs. Further study may be needed to shed light on the role of both enzymes in AA metabolism. |
Date: | 2011-06-10 |
Relation: | Toxicology Letters. 2011 Jun;203(2):118-126. |
Link to: | http://dx.doi.org/10.1016/j.toxlet.2011.03.008 |
JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0378-4274&DestApp=IC2JCR |
Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000291140400004 |
Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79955479432 |
Appears in Collections: | [劉紹興] 期刊論文
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