title: MGMT hypomethylation is associated with DNA damage in workers exposed to low-dose benzene.
abstract: OBJECTIVE
  This study aims to assess the effects of low-dose benzene on DNA damage and O6-methylguanine-DNA methyltransferase (MGMT) methylation in occupational workers.
  
  
  METHODS
  We recruited 96 nonsmoking male petrochemical industry workers exposed to low-dose benzene and 100 matched control workers. Urinary S-phenylmercapturic acid (SPMA) and S-benzylmercapturic acid (SBMA) were measured for indicating internal exposure of benzene and toluene. The degree of DNA damage was determined by the Comet assay. The levels of MGMT methylation were detected quantitatively by bisulphite-PCR pyrosequencing assay.
  
  
  RESULTS
  The benzene-exposed workers had significantly higher levels of urinary SPMA, degree of DNA damage but decreased MGMT methylation than the controls (all p < 0.05). In contrast, the level of urinary SBMA does not differ between benzene-exposed workers and the controls. In all participants, MGMT methylation was negatively associated with the urinary SPMA and the degree of DNA damage, indicating that epigenetic regulation might be involved in response to low-dose benzene exposure-induced genetic damage.
  
  
  CONCLUSIONS
  MGMT methylation could be a potent biomarker associated with low-dose benzene exposure and benzene-induced DNA damage.
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Zhini
authors.initials: Z
authors.lastname: He
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Qin
authors.affiliation: b Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment , Guangdong Province Hospital for Occupational Disease Prevention and Treatment , Guangzhou , China.
authors.forename: Zhenlie
authors.initials: Z
authors.lastname: Huang
authors.affiliation: c Key Laboratory of Chemical Safety and Health , National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention , Beijing , China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: c Key Laboratory of Chemical Safety and Health , National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention , Beijing , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: d Department of Toxicology, School of Public Health , Guangdong Medical University , Guangzhou , China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Liu
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Fangping
authors.initials: F
authors.lastname: Wang
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Daochuan
authors.initials: D
authors.lastname: Li
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zeng
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Deng
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: d Department of Toxicology, School of Public Health , Guangdong Medical University , Guangzhou , China.
authors.forename: Huanwen
authors.initials: H
authors.lastname: Tang
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: a Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health , Sun Yat-sen University , Guangzhou , China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D001554:Benzene / Q000032:analysis / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D004249:DNA Damage / Q000187:drug effects*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D019853:O(6)-Methylguanine-DNA Methyltransferase; D016273:Occupational Exposure / Q000032:analysis*; D000066388:Oil and Gas Industry; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D025521:Tumor Suppressor Proteins; C053003:S-phenyl-N-acetylcysteine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D019853:O(6)-Methylguanine-DNA Methyltransferase; D045643:DNA Repair Enzymes; D001554:Benzene; D000111:Acetylcysteine; C029319:S-benzyl-N-acetyl-L-cysteine
keywords: Benzene; DNA damage; DNA methylation; MGMT gene; biomarker