title: Significant association between decreased ALDH2 activity and increased sensitivity to genotoxic effects in workers occupationally exposed to styrene.
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.
authors.affiliation: College of Biological Science and Engineering, Fuzhou University, Fuzhou, China.|Japan National Institute of Occupational Safety and Health, Kawasaki, Japan.
authors.forename: Zuquan
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Japan National Institute of Occupational Safety and Health, Kawasaki, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Suda
authors.affiliation: College of Biological Science and Engineering, Fuzhou University, Fuzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wan
authors.affiliation: National Institute of Occupational Health and Poison Control, China CDC, Beijing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Food and Drug Administration of Beijing Fengtai District, Beijing, China.
authors.forename: Dongzhu
authors.initials: D
authors.lastname: Guan
authors.affiliation: Beijing Guoji-Zhongyi Hospital, Beijing, China.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Zhao
authors.affiliation: National Institute of Occupational Health and Poison Control, China CDC, Beijing, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Japan National Institute of Occupational Safety and Health, Kawasaki, Japan.|Present address: Department of Sport and Medical Science, Faculty of Medical Technology, Teikyo University, Tokyo, Japan.
authors.forename: Muneyuki
authors.initials: M
authors.lastname: Miyagawa
authors.affiliation: Japan National Institute of Occupational Safety and Health, Kawasaki, Japan.
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009152:Mutagenicity Tests; D009784:Occupational Diseases / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D020058:Styrene / Q000493:pharmacokinetics / Q000506:poisoning*
chemical_list: D020058:Styrene; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: ALDH2 polymorphisms; aldehyde metabolism; cancer risk; genotoxicity; styrene