Global and gene-specific promoter methylation, and micronuclei induction in lead-exposed workers: A cross-sectional study

Kan Wang, Yu Meng, Tuanwei Wang, Yuting Tu, Shiyang Gong, Guanghui Zhang, William Au, Zhaolin Xia*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


Perturbation of epigenetic regulation is a well-established mechanism for cancer but its role for lead (Pb)-associated toxicity has not been adequately investigated. We aimed to investigate whether occupational Pb exposure is associated with micronuclei (MN) frequency and to further explored the mediating roles of epigenetic gene regulation. All the Pb-exposed workers recruited from a Chinese acid battery factory, blood lead levels (BLLs) and MN frequency in lymphocytes were measured. In addition, methylation levels of seven genes (Line-1, RASSF1A, RUNX3, p16, CYP26C1, hMLH1, p15) were examined among 230 workers. Robust Poisson regression model was used to investigate the association between BLLs and MN frequency. Mediation analysis was used to explore the mediating role of specific DNA methylation. Among total 677 participants, 71% were male, median BLLs was 229.1 μg/L (P25 = 155.5, P75 = 319.3; ranged from 8.9 to 647.7 μg/L), mean MN frequency was 2.5‰ (SD = 1.8‰; ranged from 0 to 9‰). Results from base model, adjusted for age, sex, and body mass index, showed that MN frequency would increase 1.38 (95%confidential interval: 1.34, 1.43) per 100 μg/L increment in BLLs. Using categorized exposure variable analyses, a BLLs dose–response increase in MN frequency was observed: 2.74 (2.13, 3.51), 3.43 (2.73, 4.32), 4.41 (3.89, 5.01) to 6.86 (6.02, 7.81). Mediation analysis indicated that Line-1 methylation significantly mediated 3.6% of the association of BLLs with MN frequency. Occupational Pb exposure induces MN frequency in a dose–response relationship. Part of this association was mediated by Line-1 promotor methylation.

Original languageEnglish
Pages (from-to)428-434
Number of pages7
JournalEnvironmental and Molecular Mutagenesis
Issue number7
Publication statusPublished - 1 Aug 2021

Bibliographical note

Funding Information:
This work was supported by the National Basic Research Program of China (grant No. 2015CB553404) and the National Natural Science Foundation of China (grant No. 81872594). The authors would like to thank the China Scholarship Council for the scholarship to K. W.

Funding Information:
National Basic Research Program of China, Grant/Award Number: 2015CB553404; National Natural Science Foundation of China, Grant/Award Number: 81872594 Funding information

Publisher Copyright:
© 2021 Environmental Mutagen Society.


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