Association between diesel exhaust exposure and mitochondrial DNA methylation

Wei Jie Seow; Wei Hu; Yufei Dai; Roel Vermeulen; Hyang-Min Byun; Jason Y Y Wong; Bryan A Bassig; Batel Blechter; Huawei Duan; Yong Niu; George Downward; Shuguang Leng; Bu-Tian Ji; Wei Fu; Jun Xu; Kees Meliefste; Jufang Yang; Dianzhi Ren; Meng Ye; Tao Meng; Ping Bin; H Dean Hosgood; Debra T Silverman; Nathaniel Rothman; Yuxin Zheng; Qing Lan

doi:10.1093/carcin/bgac077

Association between diesel exhaust exposure and mitochondrial DNA methylation

Wei Jie Seow
, Wei Hu
, Yufei Dai
, Roel Vermeulen
, Hyang-Min Byun
, Jason Y Y Wong
, Bryan A Bassig
, Batel Blechter
, Huawei Duan
, Yong Niu
, George Downward
, Shuguang Leng
, Bu-Tian Ji
, Wei Fu
, Jun Xu
, Kees Meliefste
, Jufang Yang
, Dianzhi Ren
, Meng Ye
, Tao Meng

Ping Bin, H Dean Hosgood, Debra T Silverman, Nathaniel Rothman, Yuxin Zheng, Qing Lan

IRAS OH Epidemiology Chemical Agents

National University of Singapore and National University Health System
National Cancer Institute United States
National Institute of Occupational Health and Poison Control
Newcastle University
Qingdao University
Chaoyang Center for Disease Control and Prevention
School of Veterinary Medicine, City University of Hong Kong, Hong Kong, Hong Kong SAR.
Albert Einstein College of Medicine

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 (PM_2.5) 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 PM_2.5 exposures 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 PM_2.5 were 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.

Original language	English
Pages (from-to)	1131–1136
Number of pages	6
Journal	Carcinogenesis
Volume	43
Issue number	12
Early online date	6 Oct 2022
DOIs	https://doi.org/10.1093/carcin/bgac077
Publication status	Published - Dec 2022

Bibliographical note

Published by Oxford University Press 2022.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Displacement loop
Engine exhaust
Epidemiology
Mtdna
Mutations
Occupational-exposure
Region

Access to Document

10.1093/carcin/bgac077

bgac077Final published version, 370 KBLicence: Taverne

Cite this

Seow, W. J., Hu, W., Dai, Y., Vermeulen, R., Byun, H.-M., Wong, J. Y. Y., Bassig, B. A., Blechter, B., Duan, H., Niu, Y., Downward, G., Leng, S., Ji, B.-T., Fu, W., Xu, J., Meliefste, K., Yang, J., Ren, D., Ye, M., ... Lan, Q. (2022). Association between diesel exhaust exposure and mitochondrial DNA methylation. Carcinogenesis, 43(12), 1131–1136. https://doi.org/10.1093/carcin/bgac077

@article{c701b27729d448a0a66fe6d44911e472,

title = "Association between diesel exhaust exposure and mitochondrial DNA methylation",

abstract = "ObjectivesDiesel 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.MethodsThe 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 PM2.5 exposures with mtDNA methylation levels, adjusting for potential confounders.ResultsDEE 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 PM2.5 were also significantly and inversely associated with methylation in MT-ATP6 and MT-ATP8 genes (all P-values < 0.05).ConclusionsOur findings suggest that DEE exposure perturbs mtDNA methylation, which may be of importance for tumorigenesis.",

keywords = "Displacement loop, Engine exhaust, Epidemiology, Mtdna, Mutations, Occupational-exposure, Region",

author = "Seow, \{Wei Jie\} and Wei Hu and Yufei Dai and Roel Vermeulen and Hyang-Min Byun and Wong, \{Jason Y Y\} and Bassig, \{Bryan A\} and Batel Blechter and Huawei Duan and Yong Niu and George Downward and Shuguang Leng and Bu-Tian Ji and Wei Fu and Jun Xu and Kees Meliefste and Jufang Yang and Dianzhi Ren and Meng Ye and Tao Meng and Ping Bin and Hosgood, \{H Dean\} and Silverman, \{Debra T\} and Nathaniel Rothman and Yuxin Zheng and Qing Lan",

note = "Published by Oxford University Press 2022.",

year = "2022",

month = dec,

doi = "10.1093/carcin/bgac077",

language = "English",

volume = "43",

pages = "1131{\textendash}1136",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "12",

}

Seow, WJ, Hu, W, Dai, Y, Vermeulen, R, Byun, H-M, Wong, JYY, Bassig, BA, Blechter, B, Duan, H, Niu, Y, Downward, G, Leng, S, Ji, B-T, Fu, W, Xu, J, Meliefste, K, Yang, J, Ren, D, Ye, M, Meng, T, Bin, P, Hosgood, HD, Silverman, DT, Rothman, N, Zheng, Y & Lan, Q 2022, 'Association between diesel exhaust exposure and mitochondrial DNA methylation', Carcinogenesis, vol. 43, no. 12, pp. 1131–1136. https://doi.org/10.1093/carcin/bgac077

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 - Published by Oxford University Press 2022.

PY - 2022/12

Y1 - 2022/12

N2 - ObjectivesDiesel 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.MethodsThe 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 PM2.5 exposures with mtDNA methylation levels, adjusting for potential confounders.ResultsDEE 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 PM2.5 were also significantly and inversely associated with methylation in MT-ATP6 and MT-ATP8 genes (all P-values < 0.05).ConclusionsOur findings suggest that DEE exposure perturbs mtDNA methylation, which may be of importance for tumorigenesis.

AB - ObjectivesDiesel 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.MethodsThe 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 PM2.5 exposures with mtDNA methylation levels, adjusting for potential confounders.ResultsDEE 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 PM2.5 were also significantly and inversely associated with methylation in MT-ATP6 and MT-ATP8 genes (all P-values < 0.05).ConclusionsOur findings suggest that DEE exposure perturbs mtDNA methylation, which may be of importance for tumorigenesis.

KW - Displacement loop

KW - Engine exhaust

KW - Epidemiology

KW - Mtdna

KW - Mutations

KW - Occupational-exposure

KW - Region

U2 - 10.1093/carcin/bgac077

DO - 10.1093/carcin/bgac077

M3 - Article

C2 - 36200867

SN - 0143-3334

VL - 43

SP - 1131

EP - 1136

JO - Carcinogenesis

JF - Carcinogenesis

IS - 12

ER -

Association between diesel exhaust exposure and mitochondrial DNA methylation

Abstract

Bibliographical note

UN SDGs

Keywords

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