Oncotarget

Research Papers:

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

Zuquan Weng _, Megumi Suda, Mei Wan, Xing Zhang, Dongzhu Guan, Peiqing Zhao, Yuxin Zheng, Muneyuki Miyagawa and Rui-Sheng Wang

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Oncotarget. 2016; 7:38224-38234. https://doi.org/10.18632/oncotarget.9502

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Abstract

Zuquan Weng1,2, Megumi Suda2, Mei Wan1, Xing Zhang3, Dongzhu Guan4, Peiqing Zhao5, Yuxin Zheng3, Muneyuki Miyagawa2,6, Rui-Sheng Wang2

1College of Biological Science and Engineering, Fuzhou University, Fuzhou, China

2Japan National Institute of Occupational Safety and Health, Kawasaki, Japan

3National Institute of Occupational Health and Poison Control, China CDC, Beijing, China

4Food and Drug Administration of Beijing Fengtai District, Beijing, China

5Beijing Guoji-Zhongyi Hospital, Beijing, China

6Present address: Department of Sport and Medical Science, Faculty of Medical Technology, Teikyo University, Tokyo, Japan

Correspondence to:

Zuquan Weng, email: [email protected]

Rui-Sheng Wang, email: [email protected]

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.


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