Environ Mol Mutagen. 2021 Dec 11. doi: 10.1002/em.22469. Online ahead of print.
Diesel engine exhaust (DEE) is classified as a Group 1 human carcinogen. Using a targeted proteomics approach, we aimed to identify proteins associated with DEE and characterize these markers to understand the mechanisms of DEE-induced carcinogenicity. In this cross-sectional molecular epidemiology study, we measured elemental carbon (EC) using a personal air monitor and quantified 1317 targeted proteins in the serum using the SOMAScan assay (SOMALogic, Boulder, CA) among 19 diesel-exposed workers and 19 unexposed controls. We used linear regressions to identify proteins associated with DEE and examined their exposure-response relationship across levels of EC using linear trend tests. We further examined pathway enrichment of DEE-related proteins using MetaCore. Occupational exposure to DEE was associated with altered levels of 22 serum proteins (permutation p-value<0.01). Of these, 13 proteins (CXCL11, HAPLN1, FLT4, CD40LG, PES1, IGHE.IGK..IGL, TNFSF9, PGD, NAGK, CCL25, CCL4L1, PDXK, and PLA2G1B) showed an exposure-response relationship with EC (p-trend <0.01), with serum levels of all but PLA2G1B declining with increasing air levels of EC. For instance, CXCL11 showed the most significant association with DEE (β = -0.25; permutation p-value=0.00004), where mean serum levels were 4121.1, 2356.7, and 2298.8 relative fluorescent units among the unexposed, lower exposed (median, range: 56.9, 40.2-62.1μg/m3 ), and higher exposed (median, range: 72.9, 66.9-107.7μg/m3 ) groups, respectively (p-trend=0.0005). Pathway analysis suggested that these proteins play a role in inflammation and immunoregulation. Our study suggests that DEE exposure is associated with altered serum proteins, which play a role in inflammation and immune regulation. This article is protected by copyright. All rights reserved.
PMID:34894159 | DOI:10.1002/em.22469
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