IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

concentrations of styrene in air were 122 and 91 mg/m 3 , for the first and fourth
samplings, respectively. DNA adduct levels were determined by the 32 P-postlabelling
method in lymphocytes of laminators, and appeared to be remarkably constant (5–6
adducts/10 8 nucleotides) and significantly higher (p < 0.0001) than those in factory
controls (0.3–1 adduct/10 8 nucleotides) at all four sampling times (Vodicka et al., 1995).
Results of a three-year follow-up study continued to show significant increases in
O 6 -dG-styrene adducts in lymphocytes of lamination workers exposed to styrene
(5.9 ± 4.9 adducts/10 8 nucleotides versus 0.7 ± 0.8 adducts/10 8 nucleotides in controls)
(Vodicka et al., 1999). In this series of studies, the numbers of exposed workers and
corresponding control subjects ranged from nine to 17 individuals. The results indicate
that DNA adduct levels in lamination workers correlate with styrene exposure concentration.
Evidence from long-term studies, however, indicates that adducts do not continue
to accumulate with exposure time, suggesting that a balance is reached between adduct
formation and removal during long-term exposures. Smoking habits did not significantly
affect adduct formation in the exposed workers compared to controls.
In workers with reinforced plastics in the boat-manufacturing industry, styrene exposure
(1–235 mg/m 3 ; mean 65.6 mg/m 3 ) increased the level of an unidentified DNA
adduct (14.2 ± 2.3 adducts/10 8 nucleotides), as well as N 2 -(2-hydroxy-1-phenylethyl)-
2′-deoxyguanosine (15.8 ± 3.2 adducts/10 8 nucleotides) (Horvath et al., 1994; Rappaport
et al., 1996). Styrene exposure concentration correlated with N 2 -guanine adduct levels.
The increased formation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) adducts in
lymphocytes of styrene-exposed workers (2.23 ± 0.54 8-OHdG/10 5 dG versus
1.52 ± 0.45 8-OHdG/10 5 dG in controls) provides evidence that styrene exposure also
causes oxidative DNA damage (Marczynski et al., 1997a). It was suggested that such
damage could alter the balance of oxidants and antioxidants in the cell. This has led to a
new hypothesis for genotoxicity of styrene based on oxidative stress (Marczynski et al.,
2000).
(ii) DNA single-strand breaks
STYRENE 505
In 17 workers with low occupational exposure to styrene (time-weighted average
exposure, 29.4 mg/m 3 ), an exposure-dependent increase was seen in single-strand breaks
(IARC, 1994a). An earlier investigation of the same group of workers reported that DNA
single-strand breaks — measured by the DNA unwinding method — were also induced
in workers estimated to have higher exposure to styrene (average, 300 mg/m 3 ) calculated
from post-shift urinary mandelic acid and blood concentrations of styrene glycol (Mäki-
Paakkanen et al., 1991). Lack of persistence of the DNA damage indicated that the strand
breaks were repaired in the exposed workers. Three studies reported on DNA breakage,
measured by use of the single-cell gel electrophoresis assay, in lymphocytes of lamination
workers exposed to styrene in the reinforced-plastics industry (exposure range,
68–101 mg/m 3 ) (Vodicka et al., 1995; Somorovská et al., 1999; Vodicka et al., 1999).
Smoking habits had no effect on the level of styrene-induced DNA damage. One study