Cytogenetic biomarkers, urinary metabolites and metabolic gene polymorphisms in workers exposed to styrene

The present study comprised a biomonitoring study in 95
workers occupationally exposed to styrene and 98
unexposed controls, employing an integrated approach
involving biomarkers of exposure, effect, and susceptibility.
Airborne styrene was evaluated at workplace, and urinary
styrene metabolites, mandelic acid (MA), phenylglyoxylic
acid (PGA), vinylphenols (VPTs) and Phenylhydroxyethylmercapturic
acids (PHEMAs), were measured as
biomarkers of internal dose. Cytogenetic alterations were
evaluated by analysing the frequency of chromosomal
aberrations (CAs) and micronucleated binucleated cells
(MNBN) in peripheral blood lymphocytes. The micronucleus
assay was coupled with centromeric fluorescence
in situ hybridization to distinguish micronuclei (MN) arising
from chromosomal breakage (C – MN) from those
harboring whole chromosomes (C + MN). The possible
influence of genetic polymorphisms of xenobiotic-metabolizing
enzymes involved in styrene biotransformation
(EPHX1, GSTT1, GSTM1, GSTP1) and NAT2 on the
cytogenetic endpoints was investigated. The exposed
workers showed a significantly higher frequency of MNBN
(13.8 ± 0.5% versus 9.2± 0.4%; P <0.001) compared to
control subjects. The effect appeared to concern both
C – and C+ MN. A positive correlation was seen between
the frequency of C+ MN and urinary level of MA+ PGA
(P < 0.05) and VPTs (P < 0.001). Chromosome-type CAs
positively correlated with airborne styrene level and VPTs
(P < 0.05), whereas chromatid-type CAs correlated with
PHEMAs (P <0.05). Workers bearing GSTM1 null genotype
showed lowered levels of PHEMAs (P <0.001). The GSTT1
null genotype was associated with increased MNBN frequencies in the exposed workers (P < 0.05) and the fast
activity EPHX genotype with a moderate decrease in both
MNBN and CAs in the controls. Our results suggest that
occupational exposure to styrene has genotoxic effects
that are potentiated by the GSTT1 gene deletion.
These observations may have relevance considering
the risk of lymphatic and haematopoietic malignancies
tentatively associated with styrene exposure.