title: Occupational exposure to styrene: modulation of cytogenetic damage and levels of urinary metabolites of styrene by polymorphisms in genes CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1.
abstract: Styrene is widely used in the production of various plastics, synthetic rubber and resins. The aim of this study was to evaluate if individual polymorphisms in xenobiotic metabolizing enzymes, related with the metabolic fate of styrene, could modify individual susceptibility to the possible genotoxic effects of the styrene exposure. Twenty-eight reinforced plastic workers and 28 control subjects were studied. In the selected population the urinary styrene metabolites mandelic (MA) and phenylglyoxylic (PGA) acids were quantified, sister chromatid exchanges (SCE) and micronuclei (MN) were assessed in peripheral lymphocytes and all the subjects were genotyped for GSTM1, GSTT1 (gene deletions), GSTP1 (codon 105 ile==>val), EPHX1 (codons 113 tyr==>his and 139 his==>arg) and CYP2E1 (DraI polymorphism in intron 6). The results obtained showed a significant difference between the levels of SCE, but not in MN levels, in exposed workers as compared with the control group. The GSTP1 and CYP2E1 individual genotypes modulate the baseline levels of SCE that are lower in non-wild type individuals for both polymorphisms. The GSTM1 null individuals with low levels of exposure have significantly higher urinary levels of MA+PGA. The present data seem to suggest that apart from the methodology usually used for monitoring populations occupationally exposed to styrene (urinary metabolites and biomarkers of early biological effects) the analysis of individual genotypes associated with the metabolic fate of styrene should also be carried out in order to evaluate the individual genetic susceptibility of exposed populations.
authors.affiliation: National Institute of Health, Environmental Health and Toxicology Department, Largo 1 de Dezembro, 4000 Porto, Portugal.
authors.forename: João P
authors.initials: JP
authors.lastname: Teixeira
authors.forename: Jorge
authors.initials: J
authors.lastname: Gaspar
authors.forename: Susana
authors.initials: S
authors.lastname: Silva
authors.forename: Joana
authors.initials: J
authors.lastname: Torres
authors.forename: Susana N
authors.initials: SN
authors.lastname: Silva
authors.forename: M Conceição
authors.initials: MC
authors.lastname: Azevedo
authors.forename: Paula
authors.initials: P
authors.lastname: Neves
authors.forename: Blanca
authors.initials: B
authors.lastname: Laffon
authors.forename: Josefina
authors.initials: J
authors.lastname: Méndez
authors.forename: Carla
authors.initials: C
authors.lastname: Gonçalves
authors.forename: Olga
authors.initials: O
authors.lastname: Mayan
authors.forename: Peter B
authors.initials: PB
authors.lastname: Farmer
authors.forename: José
authors.initials: J
authors.lastname: Rueff
mesh_terms: D000293:Adolescent; D000328:Adult; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019570:Inhalation Exposure; D007527:Isoenzymes / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests; D008875:Middle Aged; D016273:Occupational Exposure; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012854:Sister Chromatid Exchange / Q000187:drug effects; D020058:Styrene / Q000009:adverse effects* / Q000378:metabolism
chemical_list: D019392:Cytochrome P-450 CYP2E1; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D020058:Styrene; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human