Archives of Toxicology

, Volume 90, Issue 8, pp 1997–2008 | Cite as

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

  • Xiao Zhang
  • Jie Li
  • Zhini He
  • Huawei Duan
  • Weimin Gao
  • Haisheng Wang
  • Shanfa Yu
  • Wen Chen
  • Yuxin ZhengEmail author
Genotoxicity and Carcinogenicity


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.


Diesel engine exhaust DNA methylation DNA damage response-related genes Hypomethylation 



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).

Compliance with ethical standards

Ethical approval

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.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

204_2015_1598_MOESM1_ESM.docx (25 kb)
Supplementary material 1 (DOCX 24 kb)
204_2015_1598_MOESM2_ESM.docx (1.4 mb)
Supplementary material 2 (DOCX 1427 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Xiao Zhang
    • 1
  • Jie Li
    • 2
  • Zhini He
    • 2
  • Huawei Duan
    • 1
  • Weimin Gao
    • 3
  • Haisheng Wang
    • 4
  • Shanfa Yu
    • 5
  • Wen Chen
    • 2
  • Yuxin Zheng
    • 1
    Email author
  1. 1.Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison ControlChinese Center for Disease Control and PreventionBeijingChina
  2. 2.Faculty of Preventive Medicine, School of Public HealthSun Yat-sen UniversityGuangzhouChina
  3. 3.Department of Environmental Toxicology, The Institute of Environmental and Human HealthTexas Tech UniversityLubbockUSA
  4. 4.Luoyang Center for Disease Control and PreventionLuoyangChina
  5. 5.Henan Institute of Occupational MedicineZhengzhouChina

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