Abstract
ALDH2 is involved in the metabolism of styrene, a widely used industrial material, but no data are available regarding the influence of this enzyme on the metabolic fate as well as toxic effects of this chemical. In this study, we recruited 329 workers occupationally exposed to styrene and 152 unexposed controls. DNA strand breaks, DNA-base oxidation in leukocytes and urinary 8-hydroxydeoxyguanosine (8-OH-dG) were assayed as biomarkers to measure genotoxic effects. Meanwhile, we examined the genetic polymorphisms, including ALDH2, EXPH1, GSTM1, GSTT1 and CYP2E1, and also analyzed the levels of styrene exposure through detecting urinary styrene metabolites and styrene concentration in air. In terms of DNA damage, the three genotoxic biomarkers were significantly increased in exposed workers as compared with controls. And the styrene-exposed workers with inactive ALDH2 *2 allele were subjected to genotoxicity in a higher degree than those with ALDH2 *1/*1 genotype. Also, lower levels of urinary styrene metabolites (MA + PGA) were observed in styrene-exposed workers carrying ALDH2 *2 allele, suggesting slower metabolism of styrene. The polymorphisms of other enzymes showed less effect. These results suggested that styrene metabolism and styrene-induced genotoxicity could be particularly modified by ALDH2 polymorphisms. The important role of ALDH2 indicated that the accumulation of styrene glycoaldehyde, a possible genotoxic intermediate of styrene, could account for the genotoxicity observed, and should be taken as an increased risk of cancer.
Highlights
Styrene is a widely used material in production of plastic, rubber, fiberglass and etc
The polymorphisms of other enzymes showed less effect. These results suggested that styrene metabolism and styrene-induced genotoxicity could be modified by ALDH2 polymorphisms
We investigated the urinary excretion of styrene metabolites and various parameters of DNA damage, and analyzed if the genetic polymorphisms of styrene-metabolizing enzymes exert any modification
Summary
Styrene is a widely used material in production of plastic, rubber, fiberglass and etc. Occupational populations may be exposed to higher concentration of styrene, especially in the reinforced plastic industry [1, 2]. Public exposure to this chemical may occur due to mainstream cigarette smoke, engine exhausts, carpets and food packaging [3,4,5,6]. Inhalation is a major route for both occupational and environmental exposure to styrene [7]. Many efforts have been made to study styrene-induced adverse health effects. In some review articles [6, 8, 9], convincing evidences have been shown that styrene induces lung cancer in mice, while evidence in humans is unclear. But not all, have shown that styrene is genotoxic. International Agency for Research on Cancer (IARC) has classified styrene in group 2B as a possible human carcinogen, and its metabolite, styrene-7,8-oxide (SO), has been classified in group 2A, probably carcinogenic to humans [10]
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