Importance of genetic polymorphisms of drug-metabolizing enzymes for the interpretation of biomakers of exposure to styrene

V. Haufroid, J. P. Buchet, S. Gardinal, S. Ghittori, M. Imbriani, A. Hirvonen, D. Lison

Research output: Contribution to journalArticle

Abstract

The objective of this study was to test the influence of genetic polymorphisms for metabolic enzymes (CYP2E1, mEH, GSTM1 and GSTT1) implicated in the biotransformation of styrene in humans on the interpretation of urinary biomarkers of exposure. Thirty workers from a fibreglass-reinforced plastics factory took part in the study. Ambient styrene concentration was determined during the whole workshift by passive sampling. Urine was collected at the end of the shift for the determination of mandelic acid (MA) and phenylglyoxylic acid (PGA) (major biotransformation pathway), N-acetyl-S-(1-phenyl-2-hydroxy)ethyl-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxy)ethyl-L-cysteine (M2) (minor metabolic pathway) and creatinine. The average airborne styrene concentration of 18.2 ppm (range: 0.9-68.9 ppm) was very close to the current threshold limit value (TLV-TWA) recently adjusted by ACGIH from 50 to 20 ppm. There was a better correlation between external and internal exposure as estimated by urinary MA + PGA (r = 0.92; p-1 creatinine, GSTM1+: 2878 μg g-1 creatinine). Multivariate regression analyses were also performed and revealed that the presence of the rare CYP2E1* 1B allele linked to TaqI polymorphism (A1/A2) was associated with increased urinary concentrations of metabolites from both pathways. Two previously described polymorphisms for the EPHX gene were also tested but seemed not really relevant for interpretation of biomarkers. In conclusion, while CYP2E1 genotyping, particularly assessment of the CYP2E1* 1B allelic status, is useful for a more accurate interpretation of the concentration of urinary biomarkers, GSTM1 genotyping is absolutely necessary when considering a biological monitoring programme based on determination of urinary mercapturic acids.

Original languageEnglish
Pages (from-to)236-249
Number of pages14
JournalBiomarkers
Volume6
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • Biological monitoring
  • Cytochrome P450 2E1
  • Epoxide hydrolase
  • Genetic polymorphisms
  • Glutathione transferase
  • Mercapturic acids
  • Styrene

ASJC Scopus subject areas

  • Biotechnology
  • Toxicology

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