International Journal of Hygiene and Environmental Health 214 (2011) 127–137 Contents lists available at ScienceDirect International Journal of Hygiene and Environmental Health journal homepage: www.elsevier.de/ijheh Low level occupational exposure to styrene: Its effects on DNA damage and DNA repair Sirilak Wongvijitsuk a,b,c , Panida Navasumrit a,c , Udomratana Vattanasit a,b,c , Varabhorn Parnlob a , Math- uros Ruchirawat a,b,c,d,∗ a Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210, Thailand b Center of Excellence on Environmental Health, Toxicology and Management of Chemicals (ETM), Bangkok 10400, Thailand c Inter-University Program in Environmental Toxicology, Technology and Management, Chulabhorn Research Institute, Asian Institute of Technology and Mahidol University, Thailand d Department of Pharmacology, Faculty of Science, Mahidol University, Phayathai, Bangkok, Thailand article info Article history: Received 12 May 2010 Received in revised form 10 September 2010 Accepted 27 September 2010 Keywords: Styrene exposure DNA damage DNA repair capacity mRNA expression of CYP2E1 hOGG1 and XRCC1 abstract The present study aimed to evaluate the effects of styrene exposure at levels below the recommended standards of the Threshold Limit Value (TLV-TWA 8 ) of 20ppm (ACGIH, 2004) in reinforced-fiberglass plastics workers. Study subjects comprised 50 exposed workers and 40 control subjects. The exposed workers were stratified by styrene exposure levels, i.e. group I (<10 ppm, <42.20 mg/m 3 ), group II (10–20 ppm, 42.20–84.40 mg/m 3 ), and group III (>20 ppm, >84.40 mg/m 3 ). The mean styrene exposure levels of exposed workers were significantly higher than those of the control workers. Biomarkers of exposure to styrene, including blood styrene and the urinary metabolites, mandelic acid (MA) and phenyl- glyoxylic acid (PGA), were significantly increased with increasing levels of styrene exposure, but were not detected in the control group. DNA damage, such as DNA strand breaks, 8-hydroxydeoxyguanosine (8-OHdG), and DNA repair capacity, were used as biomarkers of early biological effects. DNA strand breaks and 8-OHdG/10 5 dG levels in peripheral leukocytes of exposed groups were significantly higher compared to the control group (P < 0.05). In addition, DNA repair capacity, determined by the cytogenetic challenge assay, was lower in all exposed groups when compared to the control group (P < 0.05). The expression of CYP2E1, which is involved in styrene metabolism, in all styrene exposed groups, was higher than that of the control group at a statistically significant level (P < 0.05). Levels of expression of the DNA repair genes hOGG1 and XRCC1 were significantly higher in all exposed groups than in the control group (P < 0.05). In addition to styrene contamination in ambient air, a trace amount of benzene was also found but, the correlation between benzene exposure and DNA damage or DNA repair capacity was not statistically significant. The results obtained from this study indicate an increase in genotoxic effects and thus health risk from occupational styrene exposure, even at levels below the recommended TLV-TWA 8 of 20 ppm. © 2010 Elsevier GmbH. All rights reserved. Introduction Styrene is an aromatic hydrocarbon and a monomer used in the production of a variety of polymers and rubbers. The major uses of styrene are in the reinforced-fiberglass plastics industry, the butadiene–styrene rubber industry, and in polystyrene manu- facturing. Styrene, a known mutagen and possible human carcinogen (group 2B; IARC, 1994), requires metabolic activation to exert genotoxic and carcinogenic effects. Styrene is metabolized by ∗ Corresponding author at: Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Vipavadee Rangsit Highway, Lak Si, Bangkok 10210, Thailand. Tel.: +66 2 574 0615; fax: +66 2 574 0616. E-mail address: mathuros@cri.or.th (M. Ruchirawat). cytochrome P450 2E1 (CYP2E1) to styrene-7,8-oxide (SO), which is further metabolized to mandelic acid (MA) and phenylglyoxylic acid (PGA) as the major end products (Bardodej and Bardodejova, 1970). MA and PGA are the main urinary metabolites that are used as biomarkers of exposure in biological monitoring of styrene expo- sure (Apostoli et al., 1983; De Rosa et al., 1993). Reactive oxygen species (ROS) can be generated during the metabolic activation of CYP2E1 through SO. ROS can cause a variety of genotoxic effects, such as formation of DNA adducts, e.g. 8-hydroxydeoxyguanosine (8-OHdG) (Marczynski et al., 1997), as well as DNA strand breaks, sister-chromatid exchanges, micronuclei and chromosomal aber- rations in human lymphocytes (Migliore et al., 2006; Vodicka et al., 2004). ROS can also cause lipid peroxidation, protein oxidation and alter defense mechanisms such as the antioxidant system and DNA repair process. DNA strand breaks and oxidative DNA damage, such as 8-hydroxydeoxyguanosine (8-OHdG), can be used as biomarkers 1438-4639/$ – see front matter © 2010 Elsevier GmbH. All rights reserved. doi:10.1016/j.ijheh.2010.09.007