Significant association between decreased ALDH2 activity and increased sensitivity to genotoxic effects in workers occupationally exposed to styrene.

// Zuquan Weng 1, 2 , Megumi Suda 2 , Mei Wan 1 , Xing Zhang 3 , Dongzhu Guan 4 , Peiqing Zhao 5 , Yuxin Zheng 3 , Muneyuki Miyagawa 2, 6 , Rui-Sheng Wang 2 1 College of Biological Science and Engineering, Fuzhou University, Fuzhou, China 2 Japan National Institute of Occupational Safety and Health, Kawasaki, Japan 3 National Institute of Occupational Health and Poison Control, China CDC, Beijing, China 4 Food and Drug Administration of Beijing Fengtai District, Beijing, China 5 Beijing Guoji-Zhongyi Hospital, Beijing, China 6 Present address: Department of Sport and Medical Science, Faculty of Medical Technology, Teikyo University, Tokyo, Japan Correspondence to: Zuquan Weng, email: wengzq@fzu.edu.cn Rui-Sheng Wang, email: wang@h.jniosh.johas.go.jp Keywords: styrene, ALDH2 polymorphisms, aldehyde metabolism, genotoxicity, cancer risk Received: October 13, 2015      Accepted: May 01, 2016      Published: May 20, 2016 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.