Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene

The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. We studied whether the gen...

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Veröffentlicht in:Toxicology letters 2010-01, Vol.192 (1), p.34-39
Hauptverfasser: Prieto-Castelló, M.J., Cardona, A., Marhuenda, D., Roel, J.M., Corno, A.
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container_start_page 34
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creator Prieto-Castelló, M.J.
Cardona, A.
Marhuenda, D.
Roel, J.M.
Corno, A.
description The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. We studied whether the genetic polymorphisms and phenotype of CYP2E1 modulate the level of urinary styrene metabolites and if they can be used for assessing risks of occupational exposure to styrene. A population of 49 male workers exposed to styrene (average level 362.7 mg/m 3) and a control group were selected. Samples of urine, blood and buccal swab were taken to determine the urinary biological indicators (phenylglyoxylic acid and mandelic acid), to quantify mRNA of CYP2E1 in blood using RT-PCR and to analyse different polymorphisms of enzyme CYP2E1 from buccal swab. We found decreased expression of mRNA of the enzyme, as well as decreased excretion of the styrene metabolites in individuals carrying the CYP2E1*5B heterozygote allele (cl/c2) with respect to the wild-type homozygote (c1/c1), which indicates a reduction in the inducibility of the enzyme in the presence of this polymorphism. The results show that the combined effect of both the CYP2E1 phenotype, measured by the expression of the specific mRNA in blood samples, and the CYP2E1*5B allele genotype, may explain the variability of urinary excretion of the styrene metabolites.
doi_str_mv 10.1016/j.toxlet.2009.01.011
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subjects Adult
Biological and medical sciences
Blood
Buccal swab
Chemical and industrial products toxicology. Toxic occupational diseases
Cytochrome P-450 CYP2E1 - genetics
Cytochrome P-450 CYP2E1 - metabolism
Cytochrome P450 2E1
Enzymes
Excretion
Genotype
Glyoxylates - metabolism
Glyoxylates - urine
Human
Humans
Male
Mandelic Acids - metabolism
Mandelic Acids - urine
Medical sciences
Metabolites
Middle Aged
Occupational
Occupational Exposure - analysis
Phenotype
Polymorphism
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Polymorphisms
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - chemistry
RNA, Messenger - genetics
Solvents
Statistics, Nonparametric
Styrene
Styrene - pharmacokinetics
Styrenes
Toxicology
Young Adult
title Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene
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