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Associations between DNA methylation in DNA damage response-related genes and cytokinesis-block micronucleus cytome index in diesel engine exhaust-exposed workers

  • Genotoxicity and Carcinogenicity
  • Published:
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Abstract

Recently, diesel engine exhaust (DEE) was reclassified as a known carcinogen to humans. DNA methylation alterations in DNA damage response (DDR)-related genes have the potential to affect DEE exposure-related cancer risk. However, the evidence regarding the association between DEE exposure and methylation alterations in DDR-related genes is limited. In 117 DEE-exposed workers and 112 non-DEE-exposed workers, we measured urinary concentrations of six mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). We also determined the methylation levels of three DDR-related genes (p16, RASSF1A, and MGMT) and LINE-1 by bisulfite-pyrosequencing assay. We found that DEE-exposed workers exhibited significantly lower mean promoter methylation levels of p16, RASSF1A, and MGMT than non-DEE-exposed workers (all p < 0.001). In all study subjects and non-smoking workers, increasing quartiles of urinary summed OH-PAHs was associated with hypomethylation of p16, RASSF1A, and MGMT (all p < 0.05). In non-smoking workers, methylation in p16, RASSF1A, and MGMT decreased by 0.36 % [95 % confidential interval (CI): −0.60, −0.11 %], 0.46 % (95 % CI: −0.79, −0.14 %), and 0.55 % (95 % CI: −0.95, −0.15 %), respectively, in association with highest versus lowest quartile of urinary summed OH-PAHs. In addition, p16, RASSF1A, MGMT, and LINE-1 methylation levels showed negative correlations with cytokinesis-block micronucleus cytome index which was previously measured in the same workers (all p < 0.05). In conclusion, our results clearly indicated that DEE exposure and increased genetic damage were associated with hypomethylation of p16, RASSF1A, and MGMT. Future studies with larger sample size are needed to confirm these associations.

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Acknowledgments

This work was supported by the Key Program of National Natural Science Foundation of China (NSFC 81130050) and the National Key Technology Research and Development Program (2014BAI12B02).

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    Authors and Affiliations

    1. Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Rd, Beijing, 100050, China

      Xiao Zhang, Huawei Duan & Yuxin Zheng

    2. Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, 74 Zhongshan Rd 2, Guangzhou, 510080, China

      Jie Li, Zhini He & Wen Chen

    3. Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 Gilbert Drive, Lubbock, TX, 79416, USA

      Weimin Gao

    4. Luoyang Center for Disease Control and Prevention, 9 Zhenghe Rd, Luoyang, 471000, China

      Haisheng Wang

    5. Henan Institute of Occupational Medicine, Kangfuxi Street, Zhengzhou, 450052, China

      Shanfa Yu

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    1. Xiao Zhang
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    Correspondence to Yuxin Zheng.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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    Xiao Zhang and Jie Li have been contributed equally to this work.

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    Zhang, X., Li, J., He, Z. et al. Associations between DNA methylation in DNA damage response-related genes and cytokinesis-block micronucleus cytome index in diesel engine exhaust-exposed workers. Arch Toxicol 90, 1997–2008 (2016). https://doi.org/10.1007/s00204-015-1598-2

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