Association between diesel exhaust exposure and mitochondrial DNA methylation

Abstract

Background: 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, and recent studies have improved our understanding of the role played by epigenetic modifications in the mitochondrial genome on tumorigenesis. In light of these developments, 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 as a DEE surrogate, 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 and mtDNA methylation levels, adjusting for potential confounders. The associations between elemental carbon, organic carbon, and PM2.5 exposures with mtDNA methylation levels were also assessed. 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 PM2.5 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. Keywords: Diesel exhaust, mitochondrial DNA methylation