title: Association of CYP2E1, GST and mEH genetic polymorphisms with urinary acrylamide metabolites in workers exposed to acrylamide.
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 4.37 × 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.
authors.affiliation: Institute of Environmental and Occupational Health Sciences, National Yang Ming University, Taipei, Taiwan.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Huang
authors.forename: Mei-Lien
authors.initials: ML
authors.lastname: Chen
authors.forename: Saou-Hsing
authors.initials: SH
authors.lastname: Liou
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Chen
authors.forename: Shi-Nian
authors.initials: SN
authors.lastname: Uang
authors.forename: Kuen-Yuh
authors.initials: KY
authors.lastname: Wu
mesh_terms: D020106:Acrylamide / Q000506:poisoning* / Q000652:urine; D000328:Adult; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009784:Occupational Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000652:urine; D016273:Occupational Exposure / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012044:Regression Analysis
chemical_list: D020106:Acrylamide; D019392:Cytochrome P-450 CYP2E1; D004247:DNA; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1