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.
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.
Teixeira
João P
JP
National Institute of Health, Environmental Health and Toxicology Department, Largo 1 de Dezembro, 4000 Porto, Portugal.
Gaspar
Jorge
J
Silva
Susana
S
Torres
Joana
J
Silva
Susana N
SN
Azevedo
M Conceição
MC
Neves
Paula
P
Laffon
Blanca
B
Méndez
Josefina
J
Gonçalves
Carla
C
Mayan
Olga
O
Farmer
Peter B
PB
Rueff
José
J
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
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