TY - JOUR
T1 - Association between diesel exhaust exposure and mitochondrial DNA methylation
AU - Seow, Wei Jie
AU - Hu, Wei
AU - Dai, Yufei
AU - Vermeulen, Roel
AU - Byun, Hyang Min
AU - Wong, Jason Y.Y.
AU - Bassig, Bryan A.
AU - Blechter, Batel
AU - Duan, Huawei
AU - Niu, Yong
AU - Downward, George
AU - Leng, Shuguang
AU - Ji, Bu Tian
AU - Fu, Wei
AU - Xu, Jun
AU - Meliefste, Kees
AU - Yang, Jufang
AU - Ren, Dianzhi
AU - Ye, Meng
AU - Meng, Tao
AU - Bin, Ping
AU - Hosgood, H. Dean
AU - Silverman, Debra T.
AU - Rothman, Nathaniel
AU - Zheng, Yuxin
AU - Lan, Qing
N1 - Publisher Copyright:
© 2022 Oxford University Press. All rights reserved.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Objectives: Diesel exhaust is an established human carcinogen, however the mechanisms by which it leads to cancer development are not fully understood. Mitochondrial dysfunction is an established contributor to carcinogenesis. Recent studies have improved our understanding of the role played by epigenetic modifications in the mitochondrial genome on tumorigenesis. In this study, we aim to evaluate the association between diesel engine exhaust (DEE) exposure with mitochondrial DNA (mtDNA) methylation levels in workers exposed to DEE. Methods: The study population consisted of 53 male workers employed at a diesel engine manufacturing facility in Northern China who were routinely exposed to diesel exhaust in their occupational setting, as well as 55 unexposed male control workers from other unrelated factories in the same geographic area. Exposure to DEE, elemental carbon, organic carbon, and particulate matter (PM2.5) were assessed. mtDNA methylation for CpG sites (CpGs) from seven mitochondrial genes (D-Loop, MT-RNR1, MT-CO2, MT-CO3, MT-ATP6, MT-ATP8, MT-ND5) was measured in blood samples. Linear regression models were used to estimate the associations between DEE, elemental carbon, organic carbon and PM2.5exposures with mtDNA methylation levels, adjusting for potential confounders. Results: DEE exposure was associated with decreased MT-ATP6 (difference = -35.6%, P-value = 0.019) and MT-ATP8 methylation (difference = -30%, P-value = 0.029) compared to unexposed controls. Exposures to elemental carbon, organic carbon, and PM2.5were also significantly and inversely associated with methylation in MT-ATP6 and MT-ATP8 genes (all P-values < 0.05). Conclusions: Our findings suggest that DEE exposure perturbs mtDNA methylation, which may be of importance for tumorigenesis.
AB - Objectives: Diesel exhaust is an established human carcinogen, however the mechanisms by which it leads to cancer development are not fully understood. Mitochondrial dysfunction is an established contributor to carcinogenesis. Recent studies have improved our understanding of the role played by epigenetic modifications in the mitochondrial genome on tumorigenesis. In this study, we aim to evaluate the association between diesel engine exhaust (DEE) exposure with mitochondrial DNA (mtDNA) methylation levels in workers exposed to DEE. Methods: The study population consisted of 53 male workers employed at a diesel engine manufacturing facility in Northern China who were routinely exposed to diesel exhaust in their occupational setting, as well as 55 unexposed male control workers from other unrelated factories in the same geographic area. Exposure to DEE, elemental carbon, organic carbon, and particulate matter (PM2.5) were assessed. mtDNA methylation for CpG sites (CpGs) from seven mitochondrial genes (D-Loop, MT-RNR1, MT-CO2, MT-CO3, MT-ATP6, MT-ATP8, MT-ND5) was measured in blood samples. Linear regression models were used to estimate the associations between DEE, elemental carbon, organic carbon and PM2.5exposures with mtDNA methylation levels, adjusting for potential confounders. Results: DEE exposure was associated with decreased MT-ATP6 (difference = -35.6%, P-value = 0.019) and MT-ATP8 methylation (difference = -30%, P-value = 0.029) compared to unexposed controls. Exposures to elemental carbon, organic carbon, and PM2.5were also significantly and inversely associated with methylation in MT-ATP6 and MT-ATP8 genes (all P-values < 0.05). Conclusions: Our findings suggest that DEE exposure perturbs mtDNA methylation, which may be of importance for tumorigenesis.
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U2 - 10.1093/carcin/bgac077
DO - 10.1093/carcin/bgac077
M3 - Article
C2 - 36200867
AN - SCOPUS:85142200024
SN - 0143-3334
VL - 43
SP - 1131
EP - 1136
JO - Carcinogenesis
JF - Carcinogenesis
IS - 12
ER -