Association of CYP2E1, GST and mEH genetic polymorphisms with urinary acrylamide metabolites in workers exposed to acrylamide

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• 作者：Yu-Fang Huang^a ; ^b ; Mei-Lien Chen^a ; ^{mlchen@ym.edu.tw"" rel=""nofollow} ; Saou-Hsing Liou^b ; Ming-Feng Chen^b ; Shi-Nian Uang^c ; Kuen-Yuh Wu^d ; ^{kuenyuhwu@ntu.edu.tw"" rel=""nofollow} ; ^{dnaadd@ms19.hinet.net"" rel=""nofollow}
• 关键词：Acrylamide ; Genetic polymorphisms ; Cytochrome P450 2E1 ; Microsomal epoxide hydrolase ; Glutathione transferases
• 刊名：Toxicology Letters
• 出版年：2011
• 出版时间：10 June 2011
• 年：2011
• 卷：203
• 期：2
• 页码：118-126
• 全文大小：549 K

文摘

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 4.37 × 10⁻³ to 113.61 μg/m³ with a mean at 15.36 μg/m³. 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.