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Environ Res. 2017 Nov;159:452-457. doi: 10.1016/j.envres.2017.08.042. Epub 2017 Sep 18.

Effects of metal-rich particulate matter exposure on exogenous and endogenous viral sequence methylation in healthy steel-workers.

Author information

1
EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122 Milan, Italy.
2
EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122 Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
3
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
4
Department of Biomedical, Surgical and Dental Sciences, University of Milano, Via Pascal, 36-20133 Milan, Italy.
5
Occupational Medicine and Industrial Hygiene, University of Brescia, Department of Experimental and Applied Medicine, Brescia, Italy.
6
EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122 Milan, Italy. Electronic address: valentina.bollati@unimi.it.

Abstract

BACKGROUND:

Inhaled particles have been shown to produce systemic changes in DNA methylation. Global hypomethylation has been associated to viral sequence reactivation, possibly linked to the activation of pro-inflammatory pathways occurring after exposure. This observation provides a rationale to investigate viral sequence (both exogenous and endogenous) methylation in association to metal-rich particulate matter exposure. To verify this hypothesis, we chose the Wp promoter of the Epstein-Barr Virus (EBV-Wp) and the promoter of the human-endogenous-retrovirus w (HERV-w), respectively as a paradigm of an exogenous and an endogenous retroviral sequence, to be investigated by bisulfite PCR Pyrosequencing. We enrolled 63 male workers in an electric furnace steel plant, exposed to high level of metal-rich particulate matter.

RESULTS:

Comparing samples obtained in the first day of a work week (time 0-baseline, after 2 days off work) and the samples obtained after 3 days of work (time 1-post exposure), the mean methylation of EBV-Wp was significantly higher at baseline compared to post-exposure (meanbaseline = 56.7%5mC; meanpost-exposure = 47.9%5mC; p-value = 0.009), whereas the mean methylation of HERV-w did not significantly differ. Individual exposure to inhalable particles and metals was estimated based on measures in all working areas and time spent by the study subjects in each area. In a regression model adjusted for age, body mass index and smoking, PM and metal components had a positive association with EBV-Wp methylation (i.e. PM10: β = 5.99, p-value < 0.038; nickel: β = 17.82, p-value = 0.02; arsenic: β = 13.59, p-value < 0.015).

CONCLUSIONS:

The difference observed comparing baseline and post-exposure samples may be suggestive of a rapid change in EBV methylation induced by air particles, while correlation between EBV methylation and PM/metal exposure may represent a more stable adaptive mechanism. Future studies investigating a larger panel of viral sequences could better elucidate possible mechanisms and their role in pro-inflammatory pathways leading to systemic health effects.

KEYWORDS:

DNA methylation; Epstein-Barr virus; Heavy metals; Human endogenous retrovirus w; PM exposure

PMID:
28858759
DOI:
10.1016/j.envres.2017.08.042
[Indexed for MEDLINE]

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